6048 results for "canc*"

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• Lineage Heterogeneity and Plasticity in Lung Cancer

  Our previous studies found lung cancer cells harboring amplification of lineage oncogenes are specifically dependent on their expression for survival. The need for lineage amplified genes in a subset of cancers suggests unique vulnerabilities in cancer cells that may be poised on the brink of survival. However, these amplifications represent only a minor subset of the two major subtypes of lung cancers. Therefore, this study focuses on the lineage factors that are essential during the development and control cell identity in adult cells, in the remaining subsets of lung cancers. Through genome-wide profiling of a histone marks, we identified ‘super-enhancers' (SE) on lineage-defining transcription factor genes. Subsequent hierarchical clustering of lung cancer samples identified SEs specific to subsets of lung cancers. We aim to understand the significance of factors defining the lineage state of the newly defined subsets of lung cancers.

  Study phs004458

• PIGR+RORC+ Dendritic Cells (PRDCs) are an Immunomodulatory Subset Enriched in Malignant Ascites

  Malignant ascites is caused by the peritoneal dissemination of cancer and associated with a poor prognosis. We sought to identify unique features of the ascites microenvironment and leveraged single-cell RNA sequencing in patients with ascites from gastroesophageal adenocarcinoma. We identified a dendritic cell (DC) subset that expresses RORC and found that this subset exists in low abundance in human tissues but is enriched in malignant ascites from multiple tumor histologies. Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITEseq) data from ascites samples and matched PBMCs are available through dbGaP.

  Study phs004309

• Proteogenomic Analysis of CALGB40601 (ALLIANCE) a Neoadjuvant Phase III HER2-Positive Breast Cancer Trial

  80 frozen core needle biopsies from 54 HER2+ breast cancer patients from the CALGB 40601 trial (NCT00770809) were processed for proteogenomic analysis to identify genes, proteins, and phosphosites associated with pathological complete response to neodjuvant anti-HER2 therapies. The final set included 22 patients treated with trastuzumab plus lapatinib in combination with pacletaxel (THL arm), 24 patients treated with trastuzumab in combination with pacletaxel (TH arm), and 8 patients treated lapatinib in combination with pacletaxel (TL arm). Principal findings of this study included identifying negative cases misdiagnosed as HER2+ that did not respond to targeted therapy and observing higher levels of two biomarker candidates in non-pCR tumors. Mass spec-based proteomics and phosphoproteomics data generated from 75 biopsies (all 54 patients) will be made available via the Proteomic Data Commons. Whole exome- (67 biopsies from 49 patients) and RNA-sequencing (52 biopsies from 39 patients) data for the subset profiled with proteogenomics will be made available through dbGaP, but genomic and transcriptomic profiling data for the whole cohort has previously been deposited (phs001570).

  Study phs003576

• Genomic Characterization CS-MATCH-0007 Arm Z1B

  The CS-MATCH-0007 protocol is part of a collaboration between the Center for Cancer Genomics (CCG) and the Division of Cancer Treatment and Diagnosis (DCTD) to perform whole-exome sequencing and RNA sequencing using pre-and post-treatment tumor biopsy specimens from patients enrolled on a treatment arm of the NCI-MATCH Clinical Trial (EAY131). The goal of this study is to identify the molecular basis for response and resistance to targeted therapies that are matched to specific genomic alterations found in their cancers. Arm Z1B is one of the treatment sub-protocols within the NCI-MATCH Clinical Trial (EAY131) where patients with CCND1, CCND2, and/or CCND3 amplifications are treated with Palbociclib. This subprotocol is one of the treatment arms included in the CS-MATCH-0007 protocol and will provide specimens for the program including DNA from tumor tissue and whole blood.

  Study phs002180

• NCTN: A Randomized Phase III Trial of Endocrine Therapy plus Entinostat/Placebo in Patients with Hormone Receptor-Positive Advanced Breast Cancer (E2112)

  Study ID: E2112NCT Number: NCT02115282 ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Randomized Phase III Trial of Endocrine Therapy plus Entinostat/Placebo in Patients with Hormone Receptor-Positive Advanced Breast Cancer (E2112)Trial Description: This randomized phase III trial studies exemestane and entinostat to see how well they work compared to exemestane alone in treating patients with hormone receptor-positive breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or another place in the body (metastatic). Estrogen can cause the growth of breast cancer cells. Endocrine therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether exemestane is more effective with or without entinostat in treating breast cancer. Clinical data presented in the following publication(s):PMID 34357781 Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveBreast Neoplasm - Breast Neoplasm, MiscellaneousClinical dataset(s) included:NCT02115282-D1 (PMID 34357781): There are two datasets for PMID 34357781. This dataset, NCT02115282-D1, contains baseline characteristics, stratification factors, ER and PgR status, treatment, lysine acetylation, grade 5 toxicity, and efficacy data. NCT02115282-D2 (PMID 34357781): There are two datasets for PMID 34357781. This dataset, NCT02115282-D2, contains toxicity data. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004252

• Childhood Cancer Data Initiative (CCDI): Texas Pediatric Patient Derived Xenograft 

  The DNA/RNA samples of patients for which PDX models were developed were from a population of children, adolescents, and young adults from South Texas. Consent was obtained for collection of malignant and non-malignant tissue samples for genetic analysis and for the development of models to study new ways to treat cancer. For additional details, please refer to these publications: PMID: 37915590; PMID: 37990009.

  Study phs003215

• Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis (ATTRACT-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. ObjectivesTo determine whether pharmacomechanical thrombolysis prevents post-thrombotic syndrome in patients with proximal deep-vein thrombosis.BackgroundDespite the use of anticoagulant therapy, post-thrombotic syndrome develops within 2 years in approximately half of patients with proximal deep-vein thrombosis (DVT). Small randomized trials have suggested that active removal of acute thrombus may preserve venous function and prevent post-thrombotic syndrome.Pharmacomechanical catheter-directed thrombolysis (hereafter “pharmacomechanical thrombolysis”) is the delivery of a fibrinolytic drug into the thrombus with concomitant thrombus aspiration or maceration. This method is thought to be safer, more effective, and more efficient than previous methods. However, the question of whether this method improves long-term DVT patient outcomes with acceptable risk and cost had not yet been addressed.ParticipantsPatients with symptomatic proximal deep-vein thrombosis involving the femoral, common femoral, or iliac vein (with or without other involved ipsilateral veins) were enrolled at 56 clinical centers in the United States. Patients were excluded if they were younger than 16 or older than 75 years of age, were pregnant, had had symptoms for more than 14 days, were at high bleeding risk, had active cancer, had established post-thrombotic syndrome, or had had ipsilateral deep-vein thrombosis in the previous 2 years.A total of 692 patients underwent randomization. 337 patients were assigned to the pharmacomechanical-thrombolysis group and 355 patients were assigned to the control group.DesignATTRACT was a phase 3, multicenter, randomized, open-label, assessor-blinded, controlled clinical trial. Patients were randomly assigned in a 1:1 ratio to the pharmacomechanical-thrombolysis group or the control group. Randomization was stratified according to clinical center and thrombus extent. Patients in each treatment group received initial and long-term anticoagulant therapy consistent with published guidelines and were provided sized-to-fit, knee-high, elastic compression stockings providing 30 to 40 mm Hg of pressure at the 10-day follow-up visit and every 6 months.For patients in the pharmacomechanical-thrombolysis group, recombinant tissue plasminogen activator (rt-PA) at a dose of The severity of the post-thrombotic syndrome was evaluated at 6, 12, 18 and 24 months with the use of the Villalta scale and the Venous Clinical Severity Score (in both measures, higher scores indicating more severe post-thrombotic syndrome). Patient-reported health-related quality of life at baseline and 24 months was assessed with the use of the generic Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and the venous disease–specific Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) measure. Leg pain and leg swelling at baseline, 10 days, and 30 days were assessed with the use of a 7-point Likert pain scale (with higher scores indicating more severe pain) and by measuring calf circumference, respectively. Safety outcomes included bleeding, recurrent venous thromboembolism, and death, which were reported throughout follow-up and summarized through 10 days and 24 months. The clinical personnel who performed assessments of efficacy outcomes and the adjudicators of safety and efficacy outcomes were unaware of the treatment assignments.The primary outcome was development of post-thrombotic syndrome as defined by a Villalta score of 5 or higher or an ulcer in the leg with the index deep-vein thrombosis, at any time between the 6-month follow-up visit and the 24-month follow-up visit. Conclusions In conclusion, among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of post-thrombotic syndrome but did result in a higher risk of major bleeding (Vedantham S, Goldhaber SZ, Julian JA, et al., N Engl J Med. 2017;377(23):2240-2252).

  Study phs004818

• Dissecting the Role of the Microenvironment in Follicular Lymphoma Transformation

  Follicular lymphoma is a generally indolent cancer, but histologic transformation to a more aggressive histology such as diffuse large B-cell lymphoma is associated with poor outcomes. Transformation is associated with loss of the normal lymph node organizing architecture, but the precise molecular changes to the tumor microenvironment remain poorly understood. Here we applied single-cell RNA sequencing technologies on patients with indolent and transformed follicular lymphoma to identify transformation-associated signatures in the tumor, immune, and stromal microenvironment.

  Study phs004175

• Genomics Studies of AML in Patients Older than 60 Years of Age (ECOG-ACRIN Cancer Research Group's Clinical Trial e3999)

  Acute Myeloid Leukemia (AML) is a disease of old age with a median diagnosis age of 69 years (SEER data 2024). Despite progress in our field, as patients age, they suffer from worse clinical outcomes compared to younger patients. A better understanding of disease biology is needed to yield discoveries that will contribute to the identification of therapeutic vulnerabilities in this aged population, and in the long-term, result in improved survival rates. Although AML patients older than 60 are most of the patients diagnosed with this disease, few studies have solely focused on the molecular features of this disease in the aged population. This study aimed to discover the molecular features of AML patients older than 60 years of age. De-identified blood and bone marrow specimens investigated in the study were obtained from 199 AML patients enrolled in ECOG-ACRIN Cancer Research Group's e3999 clinical trial (NCT00046930). Exome capture was performed on DNA isolated from disease enriched cells and patient-matched lymphocytes as germline controls. The frequencies and co-occurrence of somatic events and features associated with clinical outcomes in this population were reported. Phenotypic data from this study cohort were submitted to the NCTN/NCORP Data Archive. It is hoped that this resource can be leveraged to address potential disease mechanisms and treatment vulnerabilities in AML patients over the age of 60.

  Study phs003773

• Cutaneous Squamous Cell Carcinoma: Integrating Germline and Somatic Alterations that Underlie Tumor Progression

  Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States, affecting over a million people annually, and with significant mortality due to metastasis. The overall scientific objective of this study is to identify and integrate novel tumor mutational data with previously characterized information on host genetic risk factors and clinical risk factors to better understand how cancer risk alleles contribute to the development of cSCCs capable of metastasis. We analyze 290 cSCCs (145 primary cSCCs) that progressed to metastasis and 145 non-metastatic primary cSCCs arising in the well characterized GERA cohort to provide a comprehensive landscape of genomic alterations in cSCCs. The aims of the study are: a) characterize the somatic genome and transcriptome of metastatic and non-metastatic cSCCs, b) integrate somatic mutational analysis with environmental exposure data, and c) develop a risk prediction tool for metastatic-cSCC that integrate genomic and clinical data.

  Study phs003681

• CSER: Evaluating Utility and Improving Implementation of Genomic Sequencing for Pediatric Cancer Patients in the Diverse Population and Healthcare Settings of Texas: The KidsCanSeq Study

  Through this Clinical Sequencing Evidence-Generating Research (CSER) with Enhanced Diversity project we are completing a clinical study (The Texas KidsCanSeq Study) comparing the results of targeted cancer panel sequencing versus genome-scale testing in pediatric cancer patients across diverse clinical settings. We will compare the targeted pediatric cancer panel to germline whole exome sequencing (WES) of unselected childhood cancer patients. We will also compare an RNA/DNA targeted pediatric cancer panel versus WES, transcriptome sequencing and copy number array of FFPE tumor samples for the subset of patients with high-risk tumors. Exome sequencing is performed from a blood or saliva sample of the pediatric age (0-18) patient. We are building on our success completing the CSER program BASIC3 exome sequencing trial (which included 60% Hispanic and African-American patients from a single large academic center) in this large multi-institutional study of an even more diverse patient population from six pediatric oncology healthcare settings across Texas. Data from the Texas KidsCanSeq study will be submitted through the CSER Data Coordinating Center for access in NIH-supported databases.

  Study phs002378

• A Randomized Phase 2 Study of Cabozantinib in Combination with Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer

  This randomized phase II trial studies how well cabozantinib s-malate and nivolumab work in treating patients with endometrial cancer that has come back (recurrent) or spread to other places in the body (advanced or metastatic). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may work better in treating endometrial cancer.PRIMARY OBJECTIVE:I. To evaluate the clinical anti-tumor activity of cabozantinib s-malate (XL184 ([cabozantinib]) and nivolumab based on progression free survival (PFS) in patients with advanced, recurrent or metastatic endometrial cancer previously treated with at least one line of platinum-based chemotherapy compared to patients receiving nivolumab alone.SECONDARY OBJECTIVES:I. To evaluate the efficacy of cabozantinib and nivolumab in terms of overall response rate (ORR) compared to nivolumab alone.II. To evaluate overall survival (OS) of patients receiving cabozantinib and nivolumab compared to patients receiving nivolumab alone.III. To evaluate the safety of combination treatment using cabozantinib and nivolumab in patients with advanced, recurrent metastatic endometrial cancer.IV. To evaluate correlation between PD-L1 expression, CD3, CD4 and CD8 infiltrates and outcome (PFS, ORR, OS).V. To compare PD-L1 expression, CD3, CD4 and CD8 infiltrates in the primary tumor (archival tissue) and in the tissue from baseline biopsy.VI. To assess activity (PFS, ORR and OS) of nivolumab alone or in combination with cabozantinib according to microsatellite instability (MSI)/mismatched repair (MMR) status.EXPLORATORY OBJECTIVES:I. To assess activity (PFS, ORR and OS) of XL184 and nivolumab in patients progressed after previous exposure to anti PD-1, PD-L1 or PD-L2 agents or crossed-over from single agent nivolumab, and in patients with diagnosis of carcinosarcoma.II. To compare microsatellite (MS) and MMR status, in the primary tumor (archival tissue) and in the tissue from baseline biopsy.III. To assess the genomic and immune-markers landscape at baseline on tumor tissue and changes in immune landscape in peripheral blood during treatment and correlate with outcome.OUTLINE: Patients are randomized to 1 of 2 arms.ARM A: Patients receive cabozantinib s-malate orally (PO) once daily (QD) on days 1-28 and nivolumab intravenously (IV) over 30 minutes on days 1 and 15, then on day 1 beginning cycle 5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.ARM B: Patients receive nivolumab as in Arm A. Patients may cross-over to Arm A at the time of disease progression. Patients undergo CT scan, MRI, and blood sample collection throughout the study and undergo biopsy at screening and optionally at follow up.In both arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up at 30-37 days, then every 8-12 weeks.

  Study phs003414

• Dietary Intervention Study in Children Follow-Up Study (DISC06-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from DISC06 include Plasma, Serum, and Whole Blood. Objectives: To examine the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults.Background: Although animal and ecologic studies have suggested a link between dietary fat and the incidence of breast cancer, previous observational studies have not yielded definitive results. In the Women's Health Initiative dietary trial, breast cancer incidence was not significantly different between the low-fat diet group and the control group. However, findings from previous studies in humans on the association between adolescent diet and breast cancer are inconsistent and self-reports of childhood diets may yield biased results. The DISC06 follow-up study explored the hypothesis that diet during adolescence may play a greater role in breast cancer risk than diet during adulthood by evaluating the longer-term effects of the DISC intervention during childhood and adolescence on subsequent biomarkers that have been associated with breast cancer risk in adults.Participants: In the original DISC study, 663 children 8-10 years old with elevated LDL-cholesterol were recruited into DISC at six clinical centers between 1988 and 1990. From 2006 to 2008, all female DISC participants, who were 25 to 29 years old at the time of the follow-up study, were invited to participate in the DISC06 follow-up study and 260 (86.4%) of the 301 females originally randomized in DISC participated.Design: The DISC06 follow-up study enrolled young adult women who had participated in the DISC dietary intervention during childhood and adolescence to examine biomarkers associated with adult breast cancer risk, including serum levels of estrogens and progesterone, breast density, and bone mineral density.Each participant attended a single clinic visit between 2006 and 2008. These follow-up data collection visits were timed to occur in the luteal phase of the menstrual cycle, 1-14 days before the anticipated start of next menses. Participants completed questionnaires that covered following topics: demographic characteristics, medical history, reproductive and menstrual histories, prescription and non-prescription drug use including extensive information on past and current hormone use, health habits including smoking and alcohol use, family history of breast cancer, and leisure physical activity. Data from three nonconsecutive 24-hour dietary recalls collected over 2 weeks were averaged to estimate nutrient intakes. Participants completed menstrual cycle calendars following visits for up to 6 weeks until the start of their next menses. Hormones were measured in serum that was collected in the morning after an overnight fast by venipuncture using standard procedures. Breast density was measured using non-contrast magnetic resonance imaging (MRI). Bone density was measured using clinical dual-energy x-ray absorptiometry (DXA) protocols. Conclusions: Results from the DISC06 follow-up study did not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density or BMD.Dorgan JF, Liu L, Klifa C, Hylton N, Shepherd JA, Stanczyk FZ, Snetselaar LG, Van Horn L, Stevens VJ, Robson A, Kwiterovich PO Jr, Lasser NL, Himes JH, Pettee Gabriel K, Kriska A, Ruder EH, Fang CY, Barton BA. Adolescent diet and subsequent serum hormones, breast density, and bone mineral density in young women: results of the Dietary Intervention Study in Children follow-up study. Cancer Epidemiol Biomarkers Prev. 2010 Jun;19(6):1545-56. doi: 10.1158/1055-9965.EPI-09-1259. Epub 2010 May 25. PMID: 20501774; PMCID: PMC2883023.

  Study phs004554

• Identifying and Understanding Drivers of Chemoresistance in Small Cell Lung Cancer

  Using patient derived models of small cell lung cancer (SCLC), either the KEAP1 gene or the USP22 gene was deleted using lentiviral expression of a vector expressing CAS9 and single guide RNA (sgRNA) targeting KEAP1 or USP22. Control vector expressing models were also generated. RNA-Seq analysis was performed to compare gene expression in tumors growing in vivo, comparing KEAP1 deleted or USP22 deleted to control tumors under saline-treated and cisplatin/etoposide-treated conditions. Similar experiments were performed overexpressing USP22 or a control vector in a USP22-deleted patient derived xenograft model of SCLC. For USP22-deleted models, we also performed CUT&TAG analyses to examine the impact of USP22 loss on histone modifications.

  Study phs004087

• Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA

  Aberrant DNA methylation plays a critical role in tumorigenesis. While DNA methylation has been used for cancer detection and classification, DNA hemi-methylation, a novel epigenetic mark has not been analyzed extensively in cancer epigenomes. Here we report a strand-specific (ss) sequencing method (MeDIP-Seq) for plasma cell free (cf) DNA (sscf-MeDIP-Seq), which can analyze both symmetrically methylated DNA regions (DMRs) as well as hemi-methylated regions (DHMRs). Using the sscf-MeDIP-Seq method, we analyzed plasma cfDNA methylomes of 271 samples from subjects with liver cancer and brain cancer and from individuals without cancer (controls). Among them, 215 samples were chosen as the discovery cohort for the identification of DMRs and DHMRs specific in each subject group and for the training of machine learning models of multi-cancer detection (MCD) using DMRs, DHMRs and DMRs+DHMRs as inputs. These models were then used to predict the 56 samples in the validation cohort. We found that models trained with DMRs+DHMRs as inputs in general outperformed models trained with DMRs or DHMRs alone, with AUROC being 0.971, 0.981, and 0.99 in predicting control, liver and brain cancer samples in the validation cohort, respectively, by the DMR+DHMR-trained models.

  Study phs003462

• Cetuximab and Nivolumab in Recurrent/Metastatic Head and Neck Cancer

  A multi-center, non-randomized, open label, phase I/II study was conducted at Moffitt Cancer Center, Ohio State University and Emory University. Early results of the clinical trial in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has been previously published, showing that the combination of cetuximab and nivolumab has manageable toxicities and is more efficacious compared to the response rate of historical cetuximab or anti-PD-1 monotherapy (Chung et al., Cancers 2021, Chung et al., Clin Cancer Res 2022). Additional exploratory correlative studies were also conducted using the clinical specimens including formalin fixed paraffin embedded (FFPE) tumors and serially collected plasma cell free DNA (cfDNA; pre-treatment, on-treatment, and time of disease progression/end of treatment). These biomarker results were correlated with the clinical data obtained from the trial patients. Evaluated molecular biomarkers include DNA and RNA-sequencing and multiple immunohistochemistry markers. Altogether, our findings indicate that p16-negative R/M HNSCC patients may have greater benefit from the combination of cetuximab and nivolumab compared to patients with p16-positive HNSCC. It is anticipated that this resource will facilitate researchers to advance the therapeutic development by further understanding of HNSCC biology and provide tools to improve the clinical outcomes in incurable R/M HNSCC.

  Study phs004268

• Perceptions, Prevalence, and Patterns of Cannabis Use among Cancer Patients in NCI-Designated Cancer Centers

  This study aimed to better understand the evolving landscape of cannabis use among patients undergoing cancer treatment across diverse geographic regions. It sought to characterize patterns of use, patient perceptions, and contextual influences such as legal status and provider engagement that affect cannabis use. Given the shifting legal environment, this study addresses a critical gap in the literature by providing data on how cancer patients integrate cannabis into their care. The available delivery methods of cannabis have also undergone dramatic changes and now include edibles, oils, tinctures, topicals, and inhaled forms. State-based policy changes are rapidly changing. Yet research on cannabis use by cancer patients across a variety of geographic settings remains limited. The extent of cannabis use, the perceived and real benefits and risks of use, potential interactions with cancer treatment and other medications, and impact on comorbid conditions are uncertain. Clinicians should be aware of the extent of use in order to assess potential drug-drug interactions, side effects, and contraindications; hence, an understanding of how cancer patients and clinicians engage in discussions about cannabis use is essential. Twelve NCI-designated cancer centers were awarded supplemental funding to conduct surveys assessing cannabis use among recently diagnosed cancer patients. Selected sites were in 8 states with varied legal status for medical and recreational cannabis use at the time of the survey. The 12 cancer centers independently received approval from their institutional review boards (IRB) and collected data from September 2021 to August 2023. Eligible participants were cancer patients or survivors who resided in their respective cancer center's catchment area. Cancer centers were responsible for sampling patients within their catchment area with the goal of 1,000 completed surveys. Ten out of 12 cancer centers drew probability samples of patients from patient lists defining their catchment area with some stratifying the sample in various ways including by cancer type, by sex, by race/ethnicity or by a combination of demographic variables.

  Study phs004046

• Sequencing of 3D Organoids Derived From Colorectal Cancer Patients

  This study focuses on the whole-exome sequencing (WES) of patient-derived organoids (PDOs) established from colorectal cancer (CRC) tumors collected at Columbia University. CRC remains a major cause of cancer-related mortality due to its metastatic progression and resistance to therapy. To model CRC at the patient level, we generated 3D organoid cultures from primary and metastatic tumors, preserving their genetic and phenotypic characteristics. The study cohort consists of 9 CRC patients with microsatellite-stable adenocarcinomas from the ascending, transverse, and descending colon, as well as the rectum, with differentiation statuses ranging from well to moderate and moderate-poor. Notably, for one patient, we generated organoids from both the primary tumor and matched liver metastases, allowing for a comparative analysis of tumor evolution. PDOs were derived from these tumors and subjected to WES at early passage to profile somatic mutations, copy number variations, and other genomic alterations to identify mutational signatures. Mutations identified in the PDOs were cross-referenced and confirmed with mutational data from the Columbia Solid Tumor Panel, which was conducted on all tumor tissues prior to organoid establishment. Molecular technologies employed include next-generation sequencing (NGS) for WES, enabling high-resolution characterization of the genomic landscape of CRC PDOs. WES of PDOs allowed us to classify tumor samples based on oncogenic mutations and mutation types, with a specific focus on PIK3CA. Notably, the efficacy of PI3Kα-specific pharmacologic inhibitors in suppressing organoid growth was dependent on the mutational status of KRAS and PIK3CA, underscoring the importance of genomic context in therapeutic response. The dataset available through dbGaP includes raw WES data from CRC PDOs.

  Study phs003965

• HINTS Geo-Coded Data 2011 (HINTS 4 Cycle 1)

  The Health Information National Trends Survey (HINTS) is a nationally representative survey which has been administered every few years by the National Cancer Institute since 2003. HINTS 4 includes four mail-mode data collection cycles over the course of three years. The first of these cycles (Cycle 1) was conducted from October 2011 through February 2012, including a total of 3,959 respondents.

  Study phs004212

• NCTN: A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients With Stage III Colon Cancer (N0147)

  Study ID: N0147NCT Number: NCT00079274Trial Title: NCTN: A Randomized Phase III Trial of Oxaliplatin (OXAL) plus 5-Fluorouracil (5-FU)/Leucovorin (CF) with or without Cetuximab (C225) after Curative Resection for Patients with Stage III Colon Cancer (N0147)Alliance for Clinical Trials in OncologySubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Description: This randomized phase III trial was originally designed to compare three different combination chemotherapy regimens to see how well they work. As of September 1, 2004, the study was expanded to a total of 6 arms (the original 3 arms (A, B, C) and 3 additional arms which were the same as the first 3 but with cetuximab) in treating patients who have undergone surgery for stage III colon cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with monoclonal antibody therapy and giving them after surgery may kill any remaining tumor cells. It was not known at the time this study was developed which combination chemotherapy regimen is more effective after surgery in treating colon cancer. This study had several key changes, based on the results of other phase III trials. As of 6/1/2005, patients no longer received irinotecan on this study and treatment arms B, C, E, and F were discontinued. Patients on arms B and C crossed to arm A. Patients on arms E and F crossed to arm D. Patients on arms C and F who had not gotten to irinotecan continued on arms A and D, respectively. As of 8/18/2008, pre-screening for Kirsten rat sarcoma (KRAS) status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. Patients on arm G were treated per physician discretion and followed for disease and survival status. KRAS was determined in a central laboratory and was process for all patients on this study. The primary endpoint of this study was modified on 8/18/2008 to focus on patients having wild-type KRAS tumors. All modifications were approved by the Central Institution Review Board, local Institutional Review Boards, NCI, and the NCCTG Data Safety Monitoring Board.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.Clinical Data presented in the following publication(s): PMID 22474202Disease type(s): Gastrointestinal Neoplasm - Colorectal CancerClinical Dataset(s) included:NCT00079274-D1 (PMID 22474202): The NCT00079274_D1.txt dataset is one of 3 datasets associated with PubMed ID 22474202. This dataset contains information on baseline characteristics (e.g., age, race, etc.), eligibility (e.g. tumor staging, etc.), follow-up status (e.g., reason treatment ended, days from randomization until last protocol therapy, etc.), response status, and KRAS status.NCT00079274-D2 (PMID 22474202): The NCT00079274_D2.txt dataset is one of 3 datasets associated with PubMed ID 22474202. This dataset contains information on overall survival, disease free survival and time to recurrence analyses.NCT00079274-D3 (PMID 22474202): The NCT00079274_D3.txt dataset is one of 3 datasets associated with PubMed ID 22474202. This dataset contains information on grade 3 or higher reported toxicity.Additional genomic data are available for this trial under phs001290.

  Study phs004241

• HiDEF-seq Single-Molecule Sequencing of Single-Strand Mismatches and Damage

  Our study sought to resolve, with single-molecule resolution, the mismatches and damage events that precede DNA mutations. Using a novel single-molecule, long-read sequencing method (HiDEF-seq) we detected base substitutions when present in either one or both DNA strands. We compared the fidelity for dsDNA mutations to that of the same samples profiled by NanoSeq duplex sequencing. We also detected cytosine deamination, a common type of DNA damage, with single-molecule resolution. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes. These samples revealed single-strand mismatch and damage signatures. Since double-strand DNA mutations are only the endpoint of the mutation process, our approach enables new studies of how mutations arise in a variety of contexts, especially in cancer and aging.The data available via dbGaP includes raw HiDEF-seq sequencing files (Pacific Biosciences subreads in BAM format), raw NanoSeq sequencing files (Illumina FASTQ format), and raw germline sequencing files (Illumina FASTQ format).The HiDEF-seq main publication contains a supplementary table with a list of accession IDs for each sample's files.

  Study phs003604

• Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to the Antibody Drug Conjugate Sacituzumab Govitecan

  Sacituzumab Govitecan (SG), a novel antibody drug conjugate (ADC) incorporating the anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 inhibitor (SN-38) payload, is the first ADC to be approved for advanced triple negative breast cancer (TNBC). However, mechanisms governing therapeutic resistance to SG are not known. We sought to identify mechanisms of de novo and acquired resistance to SG through unbiased whole-exome sequencing (WES) and RNA sequencing analysis of pre-treatment and multi-site post-progression (autopsy) tumor specimens. We examined three metastatic TNBC cases exhibiting (1) de novo progression, (2) stable disease, and (3) a deep response followed by progression, then mapped the temporal and spatial genomic evolution of acquired resistance in the responding patient. We then conducted additional pre-clinical experiments to validate the observed resistance mechanisms. TROP2 RNA and gene copy number were associated with de novo resistance, as case (1) was found to have absent TROP2 expression in all specimens, case (2) expressed TROP2, while case (3) exhibited both expression and focal genomic amplification of the TACSTD2/TROP2 locus. The genomic phylogeny tree inferred from case (3) post-progression specimens revealed one branch harboring an acquired canonical E418K resistance mutation in TOP1 (encoding topoisomerase 1) and a subsequent sub-clonal TOP1 inactivating frameshift mutation, while a distinct branch exhibited acquisition of a novel T256R missense mutation in TACSTD2 (encoding TROP2). Both the TOP1- and TACSTD2-mutant clones seeded multiple distinct metastatic sites. Through reconstitution experiments in TROP2 negative cells we found that TROP2 T256R is a stable protein with defective cell membrane localization and reduced cell surface binding by RS7 compared to wild-type TROP2. Collectively, these findings underscore TROP2 as a determinant of initial response to SG, and they reveal parallel and mutually exclusive polyclonal molecular mechanisms of acquired resistance involving the direct antibody target and drug payload target in distinct metastatic subclones of a single patient. While further research is needed to extend these novel findings, this study highlights the specificity of SG and illustrates how identifying such mechanisms will inform rational therapeutic strategies to overcome ADC resistance.  

  Study phs002555

• The Oral Mycobiome and Risk of Pancreatic Cancer

  The purpose of our study was to assess the influence of oral microbiota on the development of pancreatic cancer. Our preliminary case-control studies showed that oral carriage of a periodontal pathogen is related to increased risk for pancreatic cancer. We hypothesize that the oral bacteria and fungi are associated with risk of pancreatic cancer. We conducted a prospective study nested in two large well-established U.S. cohorts to determine whether the oral bacterial and fungal microbiome is associated with subsequent risk of pancreatic cancer.

  Study phs003994

• Bulk ATAC and RNA Sequencing of Human Breast Cancer Metastasis Samples

  Bulk RNA-Seq and ATAC-Seq were performed on a number of matched primary breast and metastatic lung/liver tissues; in addition, non-matched metastases and primaries were also sequenced. The goal of this study is to better understand the role that regulatory elements, such as enhancers, play in metastatic breast cancer.

  Study phs003363

• Blood and Marrow Transplant Clinical Trials Network - A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation (BMT CTN-1703-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To compare two graft-vs.-host-disease prophylaxis strategies in patients undergoing hematopoietic stem cell transplantation after reduced-intensity conditioning.Background: The combination of methotrexate and a calcineurin inhibitor has been the standard of care for graft-vs.-host disease (GVHD) prevention in patients undergoing allogeneic transplantation. However, acute GVHD, chronic GVHD, or both develop in more than half of these patients, resulting in complications and death.In 2013, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) launched a phase 2 clinical trial (BMT CTN 1203) comparing three different GVHD prophylaxis strategies with a contemporaneous control regimen of tacrolimus/methotrexate (Tac/MTX) in patients undergoing hematopoietic stem cell transplantation (HSCT) after reduced-intensity conditioning (RIC). That trial identified the combination of cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as the most promising regimen. BMT CTN 1703 was a phase 3 follow up study initiated to compare PTCy/Tac/MMF to Tac/MTX.Participants: Eligible participants were aged 18 years or older and undergoing their first allogeneic transplantation. Eligible diagnoses included: acute leukemia or chronic myeloid leukemia with no circulating blasts and less than 5% blasts in the bone marrow or myelodysplasia or chronic myelomonocytic leukemia with no circulating blasts and fewer than 10% blasts in the bone marrow, chronic lymphocytic leukemia or small lymphocytic lymphoma, or lymphomas that were sensitive to therapy.A total of 431 participants were enrolled and underwent randomization. 214 participants were assigned to receive experimental prophylaxis and 217 participants were assigned to receive standard prophylaxis.Design: The BMT-CTN 1703 study was a randomized, multicenter Phase 3 clinical trial. Participants with hematologic cancers were randomly assigned in a 1:1 ratio to receive PTCy/Tac/MMF (experimental prophylaxis) or Tac/MTX (standard prophylaxis). The participants underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning.The experimental prophylaxis regimen consisted of the following: cyclophosphamide (50 mg per kilogram per day on days 3 and 4 after HSCT); tacrolimus starting on day 5 (orally at a dose of 0.05 to 0.06 mg per kilogram per day or intravenously at a dose of 0.02 to 0.03 mg per kilogram per day; taper could start on day 90 with a goal of discontinuation by day 180); and mycophenolate mofetil (15 mg per kilogram per dose orally or intravenously), not to exceed 1 g thrice daily, starting on day 5 to day 35. The standard-prophylaxis regimen consisted of methotrexate (an intravenous bolus of 15 mg per square meter on day 1 and an intravenous bolus of 10 mg per square meter on days 3, 6, and 11) and tacrolimus (dose as above, starting 3 days before HSCT; taper could start on day 90 with a goal of discontinuation by day 180).The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause.Conclusions: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide/tacrolimus/mycophenolate mofetil than among those who received tacrolimus/methotrexate.

  Study phs004711

• Childhood Cancer Data Initiative (CCDI): Metastatic Osteosarcoma Spatial Profiling

  This study contains spatial transcriptional profiling of metastatic osteosarcoma specimens using the Visium platform. This work was done as part of the Childhood Cancer Data Initiative (CCDI).

  Study phs003975

• Pharmacokinetics and Pharmacogenomics of Ribociclib in Race-Based Cohorts (LEANORA)

  Underrepresented populations' participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan microarray. CYP3A5*3, CYP3A5*6, and CYP3A5*7 variants were genotyped and CYP3A5 phenotypes were constructed from these data. We observed 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve of plasma concentration versus time curve (AUC) of ribociclib did not differ between PMs (39,230 hr*ng/mL) and IM/NMs (43,546 hr*ng/mL; P=0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

  Study phs003770

• Intratumoral Heterogeneity and Clonal Evolution Induced by HPV Integration

  The human papillomavirus (HPV) genome is integrated into host DNA in most HPV-positive cancers, but the consequences for chromosomal integrity are unknown. We used continuous long-read sequencing of oropharyngeal cancers and cervical cancer cell lines to resolve structural variation induced by HPV. We discovered a previously undescribed form of structural variation, "heterocateny," characterized by diverse, interrelated, and repetitive patterns of concatemerized virus and host DNA segments within a cancer.

  Study phs003396

• NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, A Phase III Study (S0931)

  Study ID: S0931 NCT Number: NCT01120249 SWOG Cancer Research Network Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: EVEREST: EVErolimus for Renal Cancer Ensuing Surgical Therapy, a Phase III Study (S0931) Trial Description: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. PURPOSE: This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery. Clinical data presented in the following publication(s): PMID 37524096 Disease type(s): Kidney Neoplasm - Renal Cell Carcinoma Clinical Dataset(s) included: NCT01120249-D1 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). The clinical dataset contains patient-level data (one row per patient), including eligibility, evaluability, treatment, demographic, baseline information, stratification factors, and unblinding. It also contains survival, cause of death, recurrence site, biopsy, and dose modification data. NCT01120249-D2 (PMID 37524096): There are two datasets for S0931's primary publication 37524096 (-D1 and -D2). This toxicity dataset contains event-level information (one row per patient per adverse event experience on trial). You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004249

• Germline Mutations and Developmental Mosaicism Underlying EGFR-Mutant Lung Cancer

  We designed this study to examine the etiology of multiple lung tumors in EGFR-mutant non-small cell lung cancer patients who undergo surgical resection. Participants were 52-85 years old never or former smokers, who had at least 2 surgical lung tumor pathology specimens available in the Massachusetts General Hospital biobank, at least one of which had an EGFR mutation by routine clinical genotyping. 10 patients were selected, along with two patients from a family with an inherited EGFR-T790M mutation leading to multiple lung tumors. These patient tumor samples and matched normal lung samples were microdissected to collect DNA.In addition to obtaining clinical histories, we performed whole exome sequencing to evaluate the genetic profile of matched tumor and normal samples. The WES data are available on dbGaP. Our data showed increasing mutational burden and copy number alteration with increasing invasiveness, as compared to normal tissues, for the subset of samples that were assessed for tumor invasiveness. We also observed a range of numbers of shared mutations between tumors in a single patient, indicating different degrees of relatedness between lung tumors. We hope that this resource will help researchers understand non-small cell lung cancer presentations with multiple lung tumors. These data may aid in clinical decision making for such patients.

  Study phs003379

• Mayo Clinic - Fecal Microbiota and Adenomas

  Background: Adenomatous polyps are the most common precursor to colorectal cancer (CRC), the second leading cause of cancer death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. Methods: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n=233) and without (n=547). Results: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, pro-inflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Many of our findings were consistent with previously reported shifts in the gut microbiota of CRC patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. Conclusions: These data suggest that diets rich in refined sugar, protein, and lipids may lead to increased bile acid production, creating a colonic environment that promotes the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio. In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, catalyzing adenoma development and eventually CRC. Impact: This study suggests a plausible biological mechanism to explain the links between diet, shifts in the microbiota, and CRC. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of CRC and may facilitate personalized therapeutics focused on the microbiota.

  Study phs001204

• Oncogenome of Kaposi Sarcoma

  Kaposi Sarcoma (KS) is an aggressive cancer caused by the Kaposi Sarcoma Herpesvirus (KSHV/HHV-8). Individuals with immunodeficiencies, exemplified by HIV, have an elevated risk of developing KS. However, understanding of the genetic factors contributing to KS progression is still limited. To explore potential genetic alterations in KS that could offer biological or therapeutic insights, whole exome sequencing was performed on 78 KS tumors and matching normal skin samples from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. Results showed a very low mutational burden in all samples except one (median = 11 mutations), which is the smallest number of mutations found across all 33 cancer types in The Cancer Genome Atlas (TCGA). No recurrent mutations were identified. Mutational signatures included impaired DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from a single clone. The number of genome copy alterations per genome was higher in tumors from individuals without HIV and those with advanced-stage disease. This suggests that lesions that take longer to develop may accumulate more alterations, although the overall number of alterations remains low compared to other cancers. These findings suggest that KS pathogenesis differs from other cancers, with KSHV viral infection and the expression of viral oncogenes being the primary drivers of carcinogenesis, rather than clonal oncogenic transformation arising from genetic alterations of cancer-related cellular genes.

  Study phs003897

• Childhood Cancer Data Initiative (CCDI): Admixture Analysis of Acute Lymphoblastic Leukemia in African American Children: The ADMIRAL Study

  Children with substantial African ancestry are observed to have less than half the incidence of B-cell acute lymphoblastic leukemia (B-ALL) than children of other continental ancestries. The Admixture Analysis of Acute Lymphoblastic Leukemia in African American Children study (ADMIRAL) was designed to investigate genes and loci that explain the unique risk profile of African American children. Germline DNA samples were obtained from Children's Oncology Group frontline protocols, the Michigan BioTrust for Health, and various academic hospital ALL banks. Cases represented a diagnosis of B-ALL between the ages of 0-20 years, and controls were matched on birth year, sex, and maternal race/ethnicity. All participants have reported Black/African American race or substantial inferred African genetic ancestry. Altogether, 840 cases and 392 internal controls are included in this submission. All samples were genotyped on the Illumina Global Diversity Array 8v1. Phenotype information includes case/control status and reported sex.

  Study phs004222

• NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer (E5103)

  Study ID: E5103 NCT Number: NCT00433511ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer Trial Description: This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.Clinical data presented in the following publication(s): PMID 30040523PMID 30054636PMID 24584876Disease type(s): Breast Neoplasm - Breast Cancer - Invasive Clinical dataset(s) included: NCT00433511-D1 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D1, contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D2 contains toxicity data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1. NCT00433511-D2 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D2, contains toxicity data. Dataset NCT00433511-D1 contains baseline characteristics, treatment and follow up information, cardiac function measures, and efficacy data. Dataset NCT00433511-D4 contains updated time-to-event data that have undergone further data cleaning from those in NCT00433511-D1.NCT00433511-D3 (PMID 30054636): This dataset, NCT00433511-D3, contains the data used to generate the results in PubMed ID PMID: 30054636; PMCID: PMC6385891, a non-primary publication from trial NCT00433511 looking at association of circulating tumor cells with late recurrence of ER+ breast cancer. Data include limited baseline characteristics, CTC results, time-to-recurrence data, and follow-up information. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated here in this dataset for NCT00433511-D3.NCT00433511-D4 (PMID 30040523): There are three datasets for PMID 30040523 (-D1, -D2, and -D4). This dataset, NCT00433511-D4, contains updated variables ttchf, ttbev, and os that have undergone further data cleaning from those in Dataset NCT00433511-D1 which corresponds to data used to generate the results for PMID 30040523. Dataset NCT00433511-D2 contains toxicity data.NCT00433511-D5 (Unpublished): Dataset NCT00433511-D5 contains data on time to local-regional recurrence and time to distant recurrence that were collected on the trial, but not published. NCT00433511-D6 (PMID 24584876): This dataset, NCT00433511-D6, contains the data published in PMID 24584876, a publication focusing on a subgroup of patients from ECOG-ACRIN trial E5103 (women who were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy). Data includes limited patient characteristics and amenorrhea indicators. Data that are identical to those presented in NCT00433511-D1 (for the trial's primary publication, PMID 30040523) are not duplicated in the NCT00433511-D6 dataset. Additional correlative data are available for this trial under phs003201.

  Study phs004244

• CIDR: Elucidating Epigenetic Mechanisms of Racial/Ethnic Disparities in Pancreatic Cancer

  This is a nested case-control study of 689 pancreatic cancer cases and 807 matched controls from the Multiethnic Cohort Study (MEC) (see dbGaP phs002183), a diverse prospective cohort of >215,000 African American, European American, Japanese American, Latino, and Native Hawaiian individuals from Hawaii and Los Angeles. The objective of this study is to identify blood DNA methylation markers of pancreatic cancer susceptibility and to examine whether epigenetics can partially explain the racial and ethnic disparities of pancreatic cancer. Our specific aims are: 1) to identify multiethnic epigenetic markers of pancreatic cancer risk, 2) to assess whether epigenetics improves the prediction of pancreatic cancer across race and ethnicity, and 3) to evaluate whether epigenetics mediates the association between known modifiable risk factors and pancreatic cancer. The findings from this study are expected to identify potential ethnic-specific carcinogenic processes and elucidate the determinants of racial and ethnic disparities in pancreatic cancer.

  Study phs003735

• NCTN: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCTR/IMRT Followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer (RTOG-0521)

  Study ID: RTOG-0521 NCT Number: NCT00288080 NRG Oncology Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT vs AS and 3DCTR/IMRT followed by Chemotherapy with Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer (RTOG-0521) Trial Description: RATIONALE: Androgens can cause the growth of prostate cancer cells. Hormone therapy using drugs, such as leuprolide, goserelin, flutamide, or bicalutamide, may fight prostate cancer by lowering the amount of androgens the body makes. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving hormone therapy and radiation therapy together with chemotherapy is more effective than giving hormone therapy together with radiation therapy in treating prostate cancer. PURPOSE: This randomized phase III trial is studying hormone therapy and radiation therapy followed by docetaxel and prednisone to see how well it works compared to hormone therapy and radiation therapy in treating patients with localized prostate cancer. Clinical data presented in the following publication(s): PMID 30860948Disease type(s): Reproductive System Neoplasm, Male - Prostate Cancer Clinical Dataset(s) included: NCT00288080-D1 (PMID 30860948): This dataset, NCT00288080-D1, contains the data presented in the RTOG-0521 primary publication (PMID: 30860948). The dataset includes reasons for exclusion, treatment arm, baseline characteristics, treatment compliance, adverse event, survival, cause of death, biochemical failure, and distant metastases data. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004255

• P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids

  Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy defined by extensive invasion into the local tumor microenvironment and systemic metastasis. PDAC develops in a hypoxic microenvironment and adapts to survive under low oxygen conditions, including the activation of processes that may enhance the ability of cancer cells to invade locally or metastasize. Here we employ bulk RNA-sequencing of eight patient-derived organoid (PDO) cultures grown in hypoxia and normoxia to identify differentially expressed genes. PDOs were grown in Matrigel, transferred into collagen domes, then incubated in hypoxia or normoxia. Invasive organoids were individually collected from collagen domes grown in hypoxia and normoxia separately and processed for RNA-sequencing analysis. Using this dataset, prolyl 4-hydroxylase subunit alpha (P4HA1) was identified as a potential regulator of PDAC invasion in hypoxia. This dataset exists as a reference for gene expression of invasive organoids in hypoxia and normoxia.

  Study phs003961

• Utility of Pancreatic Tumor Scrapings for Organoid Development and Precision Medicine Strategies

  Patient-derived organoids (PDOs) hold promise for predicting individualized drug responses, but their establishment is often constrained by the limited availability of tumor material and prior neoadjuvant treatment. Standard PDO generation relies on dissected tissue slices from the cut surface of the tumor which may include both the invasive front, where it is postulated that more aggressive cancer cells reside, and potentially fewer viable neoplastic cells in the tumor center. This study investigates whether scraping the PDAC cut surface is a feasible method for PDO establishment compared to standard tissue samples, in order to take advantage of the potential harvesting of viable neoplastic cells from the invasive front. Tumor scrapings from 26 patients and matched tissue slices from 20 patients were collected. PDOs were successfully established from 10 tumor scrapings and 8 matched tissue slices, including 3 neoadjuvant-treated cases. Organoid histologic architecture was comparable to the surgical tumor specimens, with paired scraping and tissue slice PDOs showing genomic and transcriptomic concordance. Pharmacotyping demonstrated that scraping PDOs reliably captured patient-specific chemosensitivity, highlighting the potential for a viable alternative method to standard tissue slice PDOs. As proliferative and treatment-resistant neoplastic cells often originate from the tumor edge, increasing representation of the periphery and across the tumor may offer a more comprehensive model of invasive tumor biology, improving the clinical and research utility of PDOs.

  Study phs004385

• Randomized Phase 2 Study of Neoadjuvant Chemotherapy, Carboplatin and Paclitaxel, with or without Atezolizumab in Triple Negative Breast Cancer (TNBC)

  This phase II trial studies how well carboplatin and paclitaxel, with or without atezolizumab, before surgery works in treating patients with newly diagnosed, stage II-III triple negative breast cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carboplatin and paclitaxel with or without atezolizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

  Study phs003296

• Investigations of Genetic Variation in Families Affected by MUTYH-Associated Polyposis

  Defects in the Base-Excision Repair gene, MUTYH, are known to increase colorectal cancer risk through a recessive Mendelian pattern and raise mutation rates in both normal somatic and germline mammalian cells. In this study, we employed whole genome sequencing (WGS) of fifteen human individuals (representing 4 related families) at 50X coverage to examine germline de novo mutation rates in a large family with pathogenic MUTYH mutations and a history of colorectal cancer. We used an in vitro cell line assay to determine the family's genotype (p. Y179C/V234M, transcript NM_001128425) partially attenuates MUTYH's function. The children of mothers affected by the biallelic pathogenic genotype were associated with a moderate increase in the C>A mutation rate, but this effect was determined to be lower than previously reported mutator effects for other biallelic pathogenic MUTYH genotypes. No similar mutation rate increase was found in children of fathers with the same genotype despite calculating that we should have adequate power to detect such a mutator effect, indicating that MUTYH's role in repairing oxidative stress might be more significant in female reproductive aging than in males. We used a combination of in vitro cell line assays and bioinformatics pipelines to assess the impact of the MUTYH genotype on germline mutation rates. The study design ensures that sufficient statistical power was available to detect mutator effects in both maternal and paternal lineages. The sequencing data generated from this study include single sample genotype files derived from WGS, focusing on germline DNA. The phenotypic data at individual level and sequence data can be accessed by authorized users, facilitating further exploration of the relationship between MUTYH pathogenic variants and colorectal cancer risk.

  Study phs003554

• NCTN: Treatment of Children with All Stages of Hepatoblastoma with Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment (AHEP0731)

  Study ID: AHEP0731 NCT Number: NCT00980460Children's Oncology Group (COG) Submitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: Treatment of Children with All Stages of Hepatoblastoma with Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment (AHEP0731)Trial Description: This phase III trial studies the side effects and how well risk-based therapy works in treating younger patients with newly diagnosed liver cancer. Surgery, chemotherapy drugs (cancer fighting medicines), and when necessary, liver transplant, are the main current treatments for hepatoblastoma. The stage of the cancer is one factor used to decide the best treatment. Treating patients according to the risk group they are in may help get rid of the cancer, keep it from coming back, and decrease the side effects of chemotherapy. Clinical data presented in the following publication(s): PMID 28211941PMID 30975630 PMID 34762296PMID 35810020PMID 37073741Disease type(s): Gastrointestinal Neoplasm - Liver and Hepatobiliary Cancer Clinical Dataset(s) included: • NCT00980460-D1 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for baseline characteristics, PRETEXT grouping, surgery details, changes in AFP levels, response, relapse site, and surgical outcome plus event-free and overall survival for all evaluable patients as reported in the manuscript. Information is only provided for evaluable patients (analysiset = 1). Variables were left blank for the patients who were not evaluable (analysiset = 0). There is one row per patient. NCT00980460-D2 and -D3 contain toxicity data for this high-risk cohort. • NCT00980460-D2 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for the specific toxicities that occurred during cycles 1 through 10 for evaluable patients. Evaluable patients are defined in NCT00980460-D1 (analysiset = 1). There are multiple rows per patient depending on whether they had multiple cycles submitted. NCT00980460-D1 contains baseline characteristics and outcome data and NCT00980460-D3 contains nausea and neuropathy toxicity events for this high-risk cohort. • NCT00980460-D3 (PMID 28211941): There are three datasets (-D1 through -D3) for the AHEP0731 publication 28211941, reporting on the high-risk cohort who received Vincristine and Irinotecan. This dataset provides the information for nausea and neuropathy that occurred during cycles 1 and 2 for evaluable patients. Evaluable patients are defined in NCT00980460-D1 (analysiset = 1). There is one row per patient. NCT00980460-D1 contains baseline characteristics and outcome data and NCT00980460-D2 contains toxicities from cycles 1 through 10 for this high-risk cohort. • NCT00980460-D4 (PMID 30975630): There are two datasets (-D4 and -D5) for the AHEP0731 publication 30975630, reporting on the low-risk cohort. This dataset provides the information for eligibility, baseline characteristics, disease stage, PRETEXT grouping, surgery details, changes in AFP levels, surgical outcome event-free survival, and overall survival. Information is only provided for eligible patients (analysis01 = 1). There is one row per patient. NCT00980460-D5 contains toxicity data for the low-risk cohort. • NCT00980460-D5 (PMID 30975630): There are two datasets (-D4 and -D5) for the AHEP0731 publication 30975630, reporting on the low-risk cohort. This dataset provides the information for the specific toxicities that occurred during protocol therapy. Evaluable patients are defined in NCT00980460-D4 (analysis01 = 1). There is one row per patient/toxicity term. Each row has the maximum grade of the particular toxicity term observed during the patient's protocol treatment. NCT00980460-D4 contains baseline characteristics and outcome data for the low-risk cohort. • NCT00980460-D6 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset provides the information for all intermediate-risk patients who were enrolled on AHEP0731, up to 02/10/2020, both eligible and ineligible. It contains data presented in Figure 1 (the consort diagram), Figure 2 (Event-Free and Overall Survival of Patients with Unresectable non-Metastatic Hepatoblastoma), Table 1 (Patient Demographics for Patients with Intermediate-risk Hepatoblastoma), and the baseline characteristics, relapse sites, PRETEXT grouping, changes in AFP levels, surgery type, and evaluability for toxicity analyses. There is one row per patient. There are 105 patients in this dataset. NCT00980460-D7 contains mean percentage of target dose delivered data and NCT00980460-D8 contains toxicity data for the intermediate-risk cohort. • NCT00980460-D7 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset, NCT00980460-D7, provides the information for all eligible intermediate-risk patients enrolled on AHEP0731, up to 02/10/2020. It contains data on the mean percentage of the target dose delivered for chemotherapy. There are 195 observations in this dataset, multiple rows per patient, with proportion of target dose delivered for cisplatin, 5-FU, doxorubicin and vincristine. NCT00980460-D6 contains baseline characteristics and outcome data and NCT00980460-D8 contains toxicity data for the intermediate-risk cohort. • NCT00980460-D8 (PMID 34762296): There are three datasets (-D6 through -D8) for the AHEP0731 publication 34762296, reporting on the intermediate-risk cohort. This dataset, NCT00980460-D8, provides the information for adverse events recorded for all eligible intermediate-risk patients enrolled on AHEP0731, up to 02/10/2020. It contains data on Table 2 (Toxicities (Grade 3, 4, and 5) of Patients with Intermediate-risk Hepatoblastoma), and the information on adverse events and toxicities in the Results section of the manuscript. There are 723 observations, one for each toxicity type per patient per cycle, included in this dataset. The number of rows per patient is dependent on the number of adverse events submitted. NCT00980460-D6 contains baseline characteristics and outcome data and NCT00980460-D7 contains mean percentage of target dose delivered data for the intermediate-risk cohort. • NCT00980460-D9 (PMID 35810020): There is one dataset for the AHEP0731 publication 35810020, reporting on the very low-risk cohort. NCT00980460-D9 provides the information for the 8 very low-risk hepatoblastoma patients who were enrolled on AHEP0731. The dataset contains baseline characteristics, α-fetoprotein levels, pretext group, vascular involvement, surgical details and tumor histology from local and central review, as well as outcome data as reported in the manuscript. It is used to generate all the tables in the manuscript, (Table 1. Patient Characteristics for Children with Very Low-Risk Hepatoblastoma and Table 2. Clinical and Surgical Traits for Children with Very Low-Risk Hepatoblastoma), and Figure 2. Event-free Survival and Overall Survival of Patients with Very Low Risk Hepatoblastoma Resected at Diagnosis. There are 8 patients in this dataset. There is one row for each patient. • NCT00980460-D10 (PMID 37073741): There are two datasets (-D10 and -D11) for the AHEP0731 publication 37073741, reporting on the high-risk cohort who received Vincristine, Irinotecan, and Temsirolimus. This dataset, NCT00980460-10, provides the information of baseline characteristics, α-fetoprotein levels, α-fetoprotein and RECIST response, as well as details on recurrent disease, metastatic disease, and surgery for the 40 high-risk hepatoblastoma patients who were enrolled on AHEP0731. Tumor histologic information and pretext classification from central review are also included as well as outcome data as reported in the manuscript. It is used to generate Table 1. Characteristics of eligible patients with high-risk hepatoblastoma treated with upfront vincristine/irinotecan/temsirolimus window therapy, Table 2. Response of patients to upfront vincristine/irinotecan/temsirolimus window therapy, Table 3. Surgical outcomes for patients treated with vincristine/irinotecan/temsirolimus upfront window therapy, Figure 1. Alpha-fetoprotein (AFP) decline after two cycles of VIT (vincristine/irinotecan/temsirolimus) therapy, and Figure 2. Event-free and overall survival of patients with high-risk hepatoblastoma treated with VIT (vincristine/irinotecan/temsirolimus). There are 40 patients in this dataset. There is one row for each patient. NCT00980460-D11 contains toxicity data for this high-risk cohort. • NCT00980460-D11 (PMID 37073741): There are two datasets (-D10 and -D11) for the AHEP0731 publication 37073741, reporting on the high-risk cohort who received Vincristine, Irinotecan, and Temsirolimus. This dataset, NCT00980460-D11, provides all grade 3 and 4 adverse events while on protocol therapy for the 36 eligible high-risk hepatoblastoma patients enrolled on AHEP0731 (Supplemental Table 3. Selected Grade 3 and 4 Toxicities) as well as selected grade 3 and 4 adverse events while on protocol therapy (Table 4. Selected grade 3 and 4 toxicities for patients treated with vincristine/irinotecan/temsirolimus upfront window therapy followed by cisplatin/5-fluorouracil/vincristine/doxorubicin.). The number of rows per patient is dependent on the number of adverse events submitted. NCT00980460-D10 contains baseline characteristics and outcome data for this high-risk cohort. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004135

• The Vaginal Microbiome, Maternal Response, and Preterm Birth

  An estimated 13 million preterm births (PTBs) occur annually worldwide, and PTB is the single most significant contributing factor to neonatal morbidity and mortality. Mechanisms underlying PTB are unknown hampering development of effective prediction and prevention strategies. PTB is linked to local and distant infections and recent data suggests that vaginal bacterial microbiome early in pregnancy is associated with subsequent PTB. Viral infections behave differently during pregnancy, with common viral infections such as varicella and influenza causing much more severe disease during pregnancy and human papillomavirus, the causative virus in cervical cancer, associated with a 2-fold increased risk for PTB. However, comprehensive assessment of vaginal viral communities during pregnancy has not been performed. Lastly, although maternal inflammation is one of the leading triggers for PTB, the precise constellation of inflammatory signals is not known. We propose that examining microbial communities or host response alone is incomplete, but that their combination will lead to refined definitions of appropriate and inappropriate microbe-maternal biology and shed new light on the old problem of PTB. Our central hypothesis is that PTB can be estimated by a combination of three criteria: vaginal bacterial communities, vaginal eukaryotic viral communities, and maternal inflammatory response. We have an interdisciplinary team assembled including perinatologists, epidemiologists, virologists, and genomics informatics experts, leveraging the unique capabilities of The McDonnell Genome Institute at Washington University in St. Louis, a well-established pregnancy bio-specimen and clinical data infrastructure, and a high-PTB burdened racially diverse patient population to test this novel hypothesis. The aims of this project are: 1) to determine the ability of bacterial and viral communities in the vagina and their dynamics over time to predict PTB, and 2) to determine the ability of the host inflammatory response in the vagina in the context of microbial communities to predict PTB. The proposed research is innovative, for the first time, comprehensively characterizing the eukaryotic vaginal virome simultaneously with vaginal bacterial communities and longitudinally capturing the maternal response to these communities. We employ an efficient study design, a well-established research infrastructure, and renowned genome sequencing expertise to test a physiologically plausible but uninvestigated paradigm that bacterial and viral communities in concert with the maternal host response can predict PTB.

  Study phs003875

• A Translational, Pharmacodynamic and Pharmacokinetic Phase IB Clinical Study of Everolimus in Resectable Non-Small Cell Lung Cancer

  This phase IB clinical trial studied the pharmacodynamic changes induced by everolimus in patients with previously untreated, resectable non small cell lung cancer. Using a combination of in vivo and ex vivo assessments with FDG PET, immunohistochemistry and genomic assays, evidence of mTOR pathway perturbation was assessed in patients treated with everolimus, an allosteric mTOR inhibitor. Untreated patients served as controls for comparison. Key results from this work include a dose-dependent biologic effect of everolimus, signal of activity in RAS mutant tumors as well as near complete metabolic and pathologic response in a case of sarcomatoid lung cancer. These findings represent novel translational insights that can guide future development of mTOR inhibitors in lung cancer and other tumor types. Additionally, metabolic response and anatomic tumor shrinkage observed in a significant proportion of patients following a short of duration of therapy with everolimus suggests potential clinical utility of this agent in carefully-selected lung cancer patients.

  Study phs000829

• Health Information National Trends Survey-SEER (HINTS-SEER)

  HINTS-SEER is a cross-sectional survey that sampled cancer survivors from three different SEER cancer registries. Sampling frames of survivors from each registry were stratified by time since diagnosis and race/ethnicity, with non-malignant tumors and non-melanoma skin cancers excluded. Respondents who consented completed a self-administered questionnaire sent through the mail and resulted in a total sample of 1,234 respondents. The goal of HINTS-SEER was to better understand the communication needs and practices, information preferences, risk behaviors and cancer knowledge of cancer survivors using a modified version of the Health Information National Trends Survey (HINTS) specifically designed for cancers survivors. Demographic information on the survivors showed that over 60% of the sample was 10 or more years since diagnosis with the most common cancers being male reproductive (24.6%), female breast (23%) and melanoma (9.6%) and gastrointestinal (8.6%). De-identified data is available in SAS, SPSS, and STATA formats, as part of a data package that also includes a history document, methodology report, data analysis recommendations, and a codebook.

  Study phs004065

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Multiethnic Cohort

  The genetic basis of cardiovascular disease in individuals of non-European ancestry remains largely unknown. Availability of ethnically diverse study populations is essential to investigate the underlying causes of disease.The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to multiple common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex, inherited diseases. The Multiethnic Cohort (MEC) of the University of Hawaii Cancer Center and the University of Southern California comprises primarily five ethnic groups: Caucasians, Japanese Americans, Native Hawaiians, African Americans and Latinos. This study contains whole genome sequence data derived from participants in the MEC cohort identified as having early onset coronary artery disease.

  Study phs003499

• Proteogenomic Studies to Understand Mechanisms and Drivers of Resistance to Immunotherapies

  Immune checkpoint inhibitors (ICIs) targeting programmed death (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) produce durable responses in advanced cutaneous melanoma, yet reliable predictive biomarkers remain elusive. We performed a multi-cohort proteogenomic investigation of pre-treatment formalin-fixed paraffin-embedded (FFPE) biopsies from patients with metastatic cutaneous melanoma who later underwent either dual PD-1+CTLA-4 ICI therapy or PD-1 ICI monotherapy. Melanoma metastases of the lung, lymph node, and skin from the 3 cohorts were collected from 12 study sites in the United States, Europe, and Australia, comprising two separate PD-1+CTLA-4 ICI-treated discovery and validation cohorts ("Discovery Cohort" and "Validation Cohort 1", n=164 samples), and one PD-1 ICI monotherapy-treated validation cohort ("Validation Cohort 2", n=44 samples). Comprehensive genomic profiling was performed across the Discovery and two Validation Cohorts (across 180 individual samples) using Ribo-Erase total RNA sequencing (RNA-seq) (data generated for 173 samples), low-pass whole-genome sequencing (lpWGS) for the purpose of detecting somatic copy-number alterations (data generated for 177 samples), and a custom melanoma-focused targeted DNA sequencing panel (comprised of 86 genes, ~0.75Mb) designed to maximize the sensitivity of detecting recurrent and clinically actionable mutations (data generated for 175 samples). Pathway-level proteomic clustering identified three tumor subtypes; ICI-sensitive (immune-inflamed), ribosome-high (translationally active), and epithelial-mesenchymal transition (EMT)-like (stromal-enriched) that were reproducibly validated and showed significant PFS differences (p = 0.02–0.03) across cohorts. Subtype–outcome associations were consistent with previous immunotherapy datasets, with pooled hazard ratios ~0.5–0.8 for immune-enriched tumors. Additionally, we identified a 127-protein classifier that outperformed previously reported genomic signatures, suggesting that proteomic subtyping captured clinically relevant biology not accessible via genomics or transcriptomics alone. Our results identify potential new therapeutic vulnerabilities and lay the foundation for biomarker-driven patient stratification in combination ICI trials. Proteomic data will be made available through the National Cancer Institute's Proteomic Data Commons repository.

  Study phs004511

• A Therapeutic Vaccine for Fibrolamellar Hepatocellular Carcinoma

  Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of liver cancer affecting 33 children and young adults that is driven by a chimeric protein, DNAJ-PKAc. We conducted a phase 1 clinical trial of a therapeutic vaccine targeting DNAJ-PKAc 38 (FLC-Vac), in combination with nivolumab and ipilimumab, in children and adults with advanced FLC. Among 16 patients enrolled, 12 completed the vaccine priming phase and were evaluable for both immunological and clinical endpoints. Grade 3 treatment-related adverse events were reported by six patients (37.5%). DNAJ43 PKAc-specific T cell responses were detected in 9/12 patients after treatment. In the subset of patients who completed the initial priming phase the disease control rate (DCR) was 75% (9/12), with three partial responses (25%). All patients with clinical responses also had DNAJ-PKAc specific T cell responses, from which we identified multiple class II-restricted T cell receptors (TCRs) with specificity for DNAJ-PKAc. Correlates of response included both functional neoantigen reactivity and changes in TCR repertoire features over time. Immune escape in two patients corresponded with immune exhaustion rather than neoantigen escape or HLA loss.

  Study phs003970

• NCTN: A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (>= 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC) (E1505)

  Study ID: E1505NCT Number: NCT00324805ECOG-ACRIN Cancer Research Group Submitted in collaboration with the NCTN/NCORP Data Archive Trial Title: NCTN: A Phase III Randomized Trial of Adjuvant Chemotherapy with or without Bevacizumab for Patients with Completely Resected Stage IB (>= 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC) (E1505) Trial Description: This randomized phase III trial studies chemotherapy and bevacizumab to see how well they work compared to chemotherapy alone in treating patients with stage IB, stage II, or stage IIIA non-small cell lung cancer that was removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab also may stop the growth of non-small cell lung cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether chemotherapy is more effective with or without bevacizumab in treating non-small cell lung cancer. Clinical data presented in the following publication(s): • PMID 29129443 Disease type(s): Lung, Mediastinal and Pleural Neoplasm - Non-Small Cell Lung Cancer Clinical dataset(s) included: • NCT00324805-D1 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D1, contains baseline characteristics, stratification factors, treatment, resection type, site of recurrence, and efficacy data. • NCT00324805-D2 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D2, contains grade 2 toxicity data presented in Table 2 of the manuscript. • NCT00324805-D3 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D3, contains grades 3-5 toxicity data presented in Table 3 of the manuscript. • NCT00324805-D4 (PMID 29129443): There are four different datasets for PMID 29129443 (trial NCT00324805). This dataset, NCT00324805-D4, contains worst grade toxicity information and can be used to derive the number of patients with worst degree 1/2 toxicities (bottom row of Table 2); and the worst degree grade 3-5 events in Table 3 and Supplement. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004246

• A Phase Ib Study of Sapacitabine and Olaparib in Patients With BRCA1/2-Mutated (BRCA1/2m) Metastatic Breast Cancer

  PARP inhibitors significantly extend progression-free survival (PFS), compared to chemotherapy in patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative metastatic breast cancer, but responses are not durable. Preclinical studies suggest that sapacitabine, an oral nucleoside analog, is synergistic with PARP inhibition in cell lines harboring homologous recombination repair (HRR) defects. To translate these findings, this phase Ib study combining sapacitabine and olaparib enrolled ten patients with gBRCA1/2-mutated HER2-negative metastatic breast cancer. The recommended phase 2 dose was not determined due to hematological toxicities, mainly neutropenia and anemia. Archival tumors from responders demonstrated evidence of HRR deficiency or of high replication stress. At progression, BRCA1/2 reversion mutations associated with a microhomology-mediated end-joining (MMEJ) signature and other acquired putative non-reversion mechanisms of resistance were identified. The median PFS observed of 9.7 months, with three patients experiencing clinical benefit greater than 15 months, suggests that the addition of sapacitabine to PARP inhibition merits further investigation.

  Study phs004095

• Evaluation of the Effects of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer

  To characterize the advanced and metastatic breast tumor immune landscape and the impact of CDK4/6 inhibition on its composition and function, we used scRNA-seq to analyze tumor biopsies pre- and post- treatment with ET and the CDK4/6i, abemaciclib. Patients with ER+/HER2- advanced or metastatic breast cancer starting first- or second-line CDK4/6i with ET were enrolled in the “Impact of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2-Breast Cancer” (NCT04352777) trial. For each patient, the same lesion was biopsied prior to treatment (T1 = baseline, pretreatment) and following four weeks of continuous abemaciclib and ET (T2 = 4 weeks post-treatment). A total of 26 pre- and post-treatment tumor biopsies from diverse sites (recurrent breast and bone, liver, and lymph node metastases) from 13 patients who had varying responses to treatment were analyzed. Following tissue dissociation, positive selection of CD45+ cells was used to enrich for tumor-infiltrating immune cells. We find that genes associated with interferon response are downregulated in T cell populations and genes associated with antigen presentation were upregulated in macrophages and dendritic cells following treatment. Raw single-cell sequencing data from the 10 patients that consented to data sharing will be made available through dbGaP.

  Study phs004470

• MP2PRT-MNG: Identifying Novel Molecular Markers of Response to Radiotherapy in Meningiomas Using Samples from the RTOG-0539 (NCT00895622)

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. NRG RTOG (Radiation Therapy Oncology Group)-0539, which was a nonrandomized phase II cooperative group trial in 2009, was selected for inclusion in this program. NRG RTOG-0539 assigned patients with histologically confirmed diagnosis of meningioma to 1 of 3 risk groups based on 2007 WHO grade, resection extent, and recurrence status, and radiotherapy was given per protocol to the intermediate- and high-risk cases. Under the MP2PRT program, DNA methylation profiling, RNA sequencing, and whole exome sequencing were performed on clinical trial cases with available tissue for molecular analyte extraction and subsequent sequencing. Raw molecular data with metadata are available for this study.

  Study phs003707

• Molecular Markers of Risk of Subsequent Invasive Breast Cancer in Women with Ductal Carcinoma in Situ

  Ductal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Novel prognostic (and ultimately predictive) markers of IBC risk may emerge from assessment of expression patterns on a global scale. Our overarching goal in this study was to facilitate early detection of patients with DCIS at risk of IBC development. To this end, we conducted a nested case-control study using clinical data and archived formalin-fixed paraffin-embedded (FFPE) tissue from a large multi-center cohort of 8175 patients initially diagnosed with DCIS in community-based hospitals and health plans and followed for subsequent IBC development. Specifically, within this cohort, we observed that p16, COX-2, and MKI67 protein expression was not associated with altered risk of ipsilateral IBC. However, we did identify miRNA expression differences associated with risk of progression to subsequent IBC. Studies of this nature have the potential to lead to approaches that will help to refine identification of women with DCIS who need enhanced surveillance and early aggressive treatment.

  Study phs004440

• CIDR: Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos

  This study aims to investigate the genetic contribution to the increased risk of acute lymphoblastic leukemia (ALL) in children of Hispanic/Latino ethnicity. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed on childhood ALL cases and controls of self-reported Hispanic/Latino ethnicity from two studies: 1) the California Childhood Leukemia Study (CCLS), and 2) the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). This study will provide genome-wide SNP array data from Hispanic/Latino children, contributing to studies of the genetic etiology of childhood ALL and cancer health disparities. It will also provide data from childhood ALL cases and controls from a Hispanic/Latino population outside of the United States (i.e., Mexico). Genetic data were generated by the Center for Inherited Disease Research. Samples were genotyped using the Illumina Global Diversity Array GDA-8v1-0. Individual level genotype data will be available through dbGaP. Note that for a small number of genotyped cases in the MIGICCL study, it was later found that these were not ALL cases but were either acute myeloid leukemia (AML) or non-acute leukemia. Additional available data include demographic and birth-related variables, and patient-related data including age-at-diagnosis and leukemia immunophenotype and molecular subtypes.

  Study phs003953

• Radiology Imaging Data Containing Faces from The Cancer Imaging Archive

  Effective January 6, 2022, all radiology datasets containing images that could be used to reconstruct a 3D volume resembling a human face were put behind a controlled-access request system to mitigate potential re-identification risks emerging from advances in facial recognition tools.

  Study phs004225

• Durvalumab Plus Tremelimumab Alone or in Combination with Low-Dose or Hypofractionated Radiotherapy in Metastatic Non-Small-Cell Lung Cancer Refractory to Previous PD(L)-1 Therapy: an Open-Label, Multicentre, Randomised, Phase 2 Trial

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 1. Please see phs003294 for Cohort 2COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies / AssaysCyTOFIHCmIFOlinkRNAseqWES

  Study phs003295

• Light at Night and Prostate Cancer in the Health Professionals Follow-Up Study

  The Health Professionals Follow-Up Study (HPFS) is a prospective cohort study of men designed to evaluate hypotheses about men's health related to diet and lifestyle to the incidence of serious illnesses, such as cancer, heart disease, and other vascular diseases. It consisted of 51,529 U.S. male health professionals who were 40-75 years old at baseline in 1986 and completed a mailed six-page baseline questionnaire. Information on age, height, weight, ancestry, medications, disease history, physical activity, lifestyle factors, and diet were gathered, with follow-up questionnaires sent biennially to update information and record health outcomes with every four years to update their diet. Light at Night and Prostate Cancer project uses HPFS participants to conduct research assessing the impact of light at night on prostate cancer incidence, with follow-up from baseline in 1986 to 2016. Average annual outdoor light at night (exposure) was derived from satellite imagery data from the US Defense Meteorological Satellite Program's Operational Linescan System (maintained by the National Oceanic and Atmospheric Administration's Earth Observation Group). Prostate cancer cases (outcome) were self-reported by study participants, and then confirmed by the HPFS team through medical record and pathology report review. The data for this project are arranged in a long format, meaning that there are multiple rows for each subject ID. The various rows correspond to different questionnaire periods. Because the exposure in this dataset, light at night, and several important covariates are time-varying variables, the format of this dataset captures the variation in exposure status by questionnaire period. The outcome variables are incidence of prostate cancer, including incidence of prostate cancer clinical subtypes, such as advanced, aggressive, high- and low-grade prostate cancer. For the published study, please see Chowdhury-Paulino et al.'s 2023 publication in Cancer Epidemiology Biomarkers and Prevention entitled, “Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study.” (PMID: 37462694).

  Study phs003538

• Whole Exome Sequencing and RNA Sequencing of High Grade Serous Ovarian Cancer in Black and White Patients

  In this study, we generated new RNA and whole exome sequencing data from high-grade serous ovarian cancer tumor samples of self-identified Black and White individuals. Our RNA-Seq analysis revealed that, while the prevalence of subtypes varied across racial groups, the cluster-specific gene expression patterns were consistent. Despite these differences in subtype prevalence, the subtype-specific survival rates were similar across racial groups. Additionally, we used the WES-Seq data to characterize mutational signatures and their underlying causes in Black high-grade serous ovarian cancer (HGSC) cases, and compared the prevalence and distribution of these signatures with those in White TCGA cases.

  Study phs003632

• Dendritic Cell Redundancy Enables Priming of Anti-Tumor CD4 T Cells in Pancreatic Cancer

  Pancreatic ductal adenocarcinoma (PDAC) is resistant to current immunotherapies. Using mouse models, we achieved durable remissions and immunological memory after administration of anti-CTLA-4 and anti-PD-1. The mechanism of action involves activation of cDC2 cells and CD4 T cells. To validate these findings in humans, we collected tumor samples from patients with pancreatic cancer. We performed single-cell RNA-seq analyses to assess the abundance of cDC2 cells before and after treatment. This dataset consists of Illumina NovaSeq sequencing output (FASTQ files) from blood and tumor libraries prepared using the 10x Genomics Single Cell 5′ Immune Profiling kit. FASTQ files are provided for gene expression (GEX), TCR, and, for multiplexed samples, HTO libraries.

  Study phs004508

• Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study

  Study population The WECARE Study is an international multicenter population-based case-control study of cases with asynchronous contralateral breast cancer (CBC) and individually matched controls with unilateral breast cancer (UBC). Recruitment and data collection for the WECARE Study were conducted in two phases, herein referred to as WECARE I (2001–2004) and WECARE II (2009–2012). The study design of the first phase (WECARE I) has been described in detail elsewhere [Bernstein JL, et al 2004, PMID: 15084244]; the second phase (WECARE II) employed a nearly identical approach [Langballe R, et al 2016, PMID: 27400983]. Participants in each phase were identified through eight population-based cancer registries, including six in the United States that contribute to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program: Los Angeles County Cancer Surveillance Program; Cancer Surveillance System of the Fred Hutchinson Cancer Center (Seattle region, WA); State Health Registry of Iowa; Cancer Surveillance Program of Orange County/San Diego-Imperial Organization for Cancer Control (Orange County/San Diego, CA); the Greater Bay Area Cancer Registry (San Francisco Bay Area region and Santa Clara region, CA); and the Sacramento and Sierra Center Registry (Sacramento region, CA). Participants were additionally identified using the Ontario Cancer Registry (Canada) and the Danish Breast Cancer Cooperative Group Registry, supplemented by data from the Danish Cancer Registry. The study protocol was approved by the institutional review or regulatory ethics boards at each study site. Data collection Study participants were interviewed by telephone using a structured questionnaire aimed at evaluating known or suspected breast cancer risk factors, including personal demographics, medical history, menstrual and reproductive history, family history of cancer, use of hormones, smoking, and alcohol intake. Risk factor status was assessed during the period prior to first diagnosis, as well as between first diagnosis and reference date (i.e., the at-risk period for CBC). Detailed data on treatment and tumor characteristics were obtained directly from cancer registry records or by abstracting medical records, including pathology and surgical reports, radiation oncology clinic notes, and systemic adjuvant treatment data. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Biospecimens were collected from study participants for genotyping: blood collected from WECARE I women; and saliva collected from WECARE II women.

  Study phs003945

• Genomic Landscape of Colorectal Cancer in a Multi-Ancestry Cohort

  Elucidating the tumor mutational landscape of colorectal cancer (CRC) in admixed and ancestrally diverse populations is essential to enable precision medicine advancements that benefit individuals of all backgrounds. This study draws from the Latino Colorectal Cancer Consortium (LC3) and other prior initiatives to characterize and examine the somatic mutational patterns of colorectal tumors in Hispanic/Latino/Latina patients (henceforth referred to as Latino) as compared to other racial and ethnic populations. It includes paired tumor-normal whole-exome sequencing from 718 patients with primary CRC (128 Latino and 469 non-Latino individuals) to investigate the associations between somatic mutational features and both self-reported ethnicity and genetic ancestry. Somatic mutations and inherited variants were called, and global genetic ancestry proportions (African, Asian, European, Native American) were estimated from inherited variants using ADMIXTURE based on reference samples from the 1000 Genomes Project (1KGP) and the Population Architecture using Genomics and Epidemiology (PAGE) Study. Associations between genetic ancestry and gene-level mutational status, microsatellite instability status, and tumor mutational burden were estimated using logistic regression, after adjusting for age at diagnosis, sex, tumor location, and stage.

  Study phs003464

• NCTN: A Phase 1/2 Study of CPX-351 (NSC# 775341) Alone followed by Fludarabine, Cytarabine, and G-CSF (FLAG) for Children with Relapsed Acute Myeloid Leukemia (AML) (AAML1421)

  Study ID: AAML1421NCT Number: NCT02642965 Children's Oncology Group (COG)Submitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Phase 1/2 Study of CPX-351 (NSC# 775341) Alone followed by Fludarabine, Cytarabine, and G-CSF (FLAG) for Children with Relapsed Acute Myeloid Leukemia (AML) (AAML1421)Trial Description: This phase I/II trial studies the side effects and best dose of liposome-encapsulated daunorubicin-cytarabine when given with fludarabine phosphate, cytarabine, and filgrastim and to see how well they work in treating younger patients with acute myeloid leukemia that has come back after treatment (relapsed) or is not responding to treatment (is refractory). Liposome-encapsulated daunorubicin-cytarabine is made up of two chemotherapy drugs, cytarabine and daunorubicin hydrochloride, and works to stop cancer cell growth by blocking the cells from dividing. Drugs used in chemotherapy, such as fludarabine phosphate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Filgrastim may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving liposome-encapsulated daunorubicin-cytarabine followed by fludarabine phosphate, cytarabine, and filgrastim may be a better treatment for patients with relapsed acute myeloid leukemia and may cause fewer side effects to the heart, a common effect of other chemotherapy treatments for acute myeloid leukemia. Clinical data presented in the following publication(s): PMID 32401633 Disease type(s): Hematopoietic Neoplasm/Leukemia - Acute Myeloid LeukemiaClinical Dataset(s) included: NCT02642965-D1 (PMID 32401633): There is 1 dataset for AAML1421's primary publication, PMID 32401633. The NCT02642965-D1 dataset is a patient level dataset (single row per patient) containing patient characteristics, cytogenetic categories, tumor response, survival, neutrophil count recovery, toxicity, residual disease status, and pharmacokinetic data for eligible pediatric acute myeloid leukemia (AML) patients enrolled on the AAML1421 clinical trial.You are encouraged to view the PDF data dictionaries found in the "Documents" tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004160

• Whole Genome Sequencing of Locally Advanced Esophageal Cancer

  We assembled a cohort of 36 patients with locally advanced esophageal cancer undergoing curative-intent therapy. Two ultrasensitive, tumor-informed, mutation enrichment sequencing tests were applied to serially collected blood samples to detect circulating tumor DNA (ctDNA), MAESTRO-Pool of the Broad Institute and the Oncodetect V2 assay (based on MAESTRO) of Exact Sciences. Both assays showed highly concordant results, with the Oncodetect V2 assay showing better sensitivity while maintaining high specificity. We found ctDNA detection postoperatively was strongly associated with disease recurrence and that most ctDNA-positive samples had variant allele fractions below 100 parts-per-million, the limit of detection of first-generation assays. Here we provide whole genome sequencing of matched tumor tissue and normal germline DNA from these 36 patients that were used to design individualized assays for MAESTRO-Pool and the Oncodetect V2 assay.

  Study phs004613

• NCI's Collection of Datasets for Pediatric and Adolescent and Young Adults Research

  This collection contains a compilation of NIH authorized individual-level datasets on childhood cancers currently in dbGaP with various data use limitations (DULs) such as Pediatric Cancer Research without the NPU modifier. The collection has been created to streamline access to pediatric, and adolescent and young adults (AYA) cancer datasets under the purview of NCI DAC and other NIH IC DACs with permission and will include any additional authorized individual-level datasets as they become available. To request access to this study collection, select phs003964 in the dbGaP Authorized Access System.

  Study phs003964

• Germline EGFR T790M and Lung Cancer Risk

  We performed germline whole-genome sequencing from peripheral blood of individuals carrying the EGFR T790M variant (n=53) and those who do not (n=206). This data is subset to chromosome 7 for all participants. For more information on study protocol please see NCT05587439.

  Study phs004412

• Genomic Sequencing of Ewing Sarcoma

  Pediatric Ewing sarcoma is a pediatric cancer that primarily arises from the bone. It is characterized by chimeric fusions of the EWS gene and an ETS family transcription factor. In this study, we performed massively parallel sequencing of a larger collection of Ewing sarcoma tumors to define the genomic landscape of this disease. We found that these tumors are among of the most genetically normal cancers currently characterized. There was also a marked absence of recurrent mutations in immediately targetable signaling transduction pathway genes. In this study we answer outstanding questions about ETS transcription factor expression, effects of treatment on mutational burden in Ewing sarcoma tumors, and describe patterns of tumor evolution. We also found that loss-of-function mutations in STAG2 were present in approximately 15% of Ewing sarcoma tumors and loss of STAG2 expression was associated with disease metastasis in this patient cohort.

  Study phs000804

• MP2PRT: Discovering Biomarkers of Outcome: EBV DNA Quantification and the Relationship of EBV and LINE1 Retrotransposon Expression in Pediatric Patients With Nasopharyngeal Carcinoma (NPC) Enrolled on ARAR0331

  Nasopharyngeal carcinoma (NPC) is a malignant neoplasm of epithelial cells. Plasma Epstein-Barr Virus (pEBV) DNA levels have been found to correlate with treatment response and survival in both pediatric and adult NPC. A completed Children's Oncology Group (COG) clinical trial, ARAR0331, treated pediatric NPC patients with induction chemotherapy followed by chemoradiotherapy with excellent survival. In this study, >95% of patients had EBV positive tumors. As a secondary objective of ARAR0331, plasma was collected at multiple time points throughout therapy to evaluate pEBV, but the analysis had not been completed as part of ARAR0331. ARAR0331 showed a higher proportion of adolescents and more Black patients, compared to White or Asian, providing a unique opportunity to compare racial subgroups. Unfortunately, patients treated on ARAR0331 had significant morbidity from treatment toxicity. Therefore, the next clinical trial will be aimed at reducing this toxicity. Discovering biomarkers of outcome is critical to correctly assigning patients to treatment groups. With support from the Cancer Moonshot Molecular Profiling to Predict Response to Treatment (MP2PRT) program, our primary analyses evaluated use of pEBV to predict outcomes or response to treatment using specimens from ARAR0331. In secondary analyses, we are evaluating EBV RNA expression using RNA in situ hybridization and LINE1 retrotransposon using immunohistochemistry. We are analyzing tumor mutations and investigation of L1TD1 and EBV insertion via whole genome sequencing (WGS). We also processed tumor specimens using single nuclei sequencing, RNA exome and multiplex immunofluorescence to evaluate immune response and spatial relationships of immune and tumor cells. Understanding NPC tumors and their immune microenvironment will help us improve future clinical trials.

  Study phs003092

• Somatic Mutations in 3,929 HPV-Positive Exfoliated Cervical Cell Samples

  We investigated the detection, timing, and HPV type specificity of cervical somatic hotspot mutations (i.e., previously reported cancer driver mutations) in 3,929 HPV-positive exfoliated cervical cell samples from individuals undergoing routine cervical screening in the U.S. using deep-targeted sequencing of 20 candidate genes. Our study included samples from 3,351 women with the following infection outcomes: 1,478 HPV16-, HPV18- and/or HPV45-positive controls (i.e., HPV infections that did not progress to precancer and/or subsequently cleared), 1,712 cervical precancers, and 161 invasive cervical cancers. We utilized residual exfoliated cervical cell samples from women routinely screened for cervical cancer precursors at Kaiser Permanente Northern California (KPNC) as part of the prospective KPNC-NCI HPV Persistence and Progression (PaP) cohort. We included 3,929 samples collected from these 3,351 women, including 974 serial sample from 396 women collected prior to their most recent screening visit to evaluate somatic hotspot mutation detection prior to diagnosis.

  Study phs003691

• Carolina Breast Cancer Study (CBCS)

  The Carolina Breast Cancer Study (CBCS), phase III, is a population-based study aiming to understand the social and molecular correlates of breast cancer outcomes, particularly among Black and young women. CBCS recruited first primary breast cancer cases from 44 North Carolina counties between 2008-2013. All cases were between age 20 and 74 and self-identified as female. Black women and young women were systematically oversampled by randomized recruitment such that the study includes approximately 50% Black women and approximately 50% women diagnosed before age 50. A total of 2,998 participants were enrolled. In the ten years following diagnosis, women completed surveys approximately every 1-2 years and diagnoses of subsequent distant local recurrence and second primary tumors were ascertained via linked medical records. We identified records of women who developed secondary breast tumors (including second primary tumors, contralateral breast cancers, and locoregional recurrences), and these participants were oversampled for targeted DNA sequencing using the UNCseq panel (~1200 genes).CBCS germline pathogenic mutations cannot be investigated because participants were consented between 2008 and 2013 with specific language prohibiting this. However, germline data can be used to call somatic mutations or to standardize somatic genomic data.For sharing of study data not included here, please visit unclineberger.org for instructions on submitting a data use agreement.

  Study phs003725

• Profiling Genome-Wide Circulating ncRNAs for the Early Detection of Lung Cancer

  Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Although imaging techniques such as low-dose computed tomography (LDCT), combined with tissue biopsies, have improved early detection rates, current diagnostic approaches are often limited by high false-positive rates, invasiveness, and radiation exposure, which lead to misdiagnosis and increased patient burden. Therefore, there is an urgent need for minimally invasive, accurate, and safe diagnostic biomarkers, particularly those derived from liquid biopsies such as blood-based exosomal RNA.This dataset specifically focuses on plasma-derived exosomal small non-coding RNAs (sncRNAs).A total of 233 de-identified plasma samples were obtained from Rush University Medical Center, including 116 NSCLC patients and 117 non-cancer controls. Exosomes were isolated from plasma, RNA was extracted, and small RNA sequencing was performed using the Illumina NextSeq 500 platform. Data available through dbGaP include individual-level raw sequencing files (FASTQ) and basic phenotype annotations of the plasma cohort.A diagnostic model was initially developed using small RNA-seq data from 1,446 tissue samples obtained from TCGA and GEO, identifying a robust sncRNA signature that distinguished NSCLC from non-cancer samples with an AUC of 0.90 in hold-out tissue validation. This signature was subsequently validated in the plasma exosome cohort, achieving an AUC of 0.84 in independent validation. The model demonstrated consistent diagnostic performance across subgroups stratified by age, sex, smoking history, cancer stage, and NSCLC subtype. Survival and functional analyses further supported the clinical and biological relevance of the identified sncRNAs. It is hoped that this resource will contribute to a better understanding of the sncRNA expression landscape in NSCLC and promote the development of non-invasive biomarkers for early cancer detection. These data may be applied to the investigation of transcriptomic and other risk factors, provide insight into cancer screening, tumor progression mechanisms, and prognosis prediction, and ultimately support precision medicine for NSCLC.

  Study phs004166

• Cancer-Restricted Cryptic Antigens Are Targets for T Cell Recognition

  Subjects included patients with pancreatic cancer, at least 18 years of age, who were recruited from outpatient clinics and inpatient units at Dana-Farber Cancer Institute and Brigham and Women's Hospital.Bulk and single-cell transcriptomic profiling of human pancreatic cancer patient samples (direct from tumor or profiling of patient-derived organoids) was performed. Patient-derived pancreatic cancer organoids were profiled in the presence or absence of interferon-gamma stimulation. Healthy-donor CD8 T lymphocytes were ex vivo primed and expanded with candidate non-canonical (cryptic) peptide antigens. Single-cell transcriptomic profiling with paired T cell receptor (TCR) sequencing and molecularly-barcoded HLA tetramers enabled deconvolution and identification of cryptic antigen-reactive TCRs.

  Study phs003887

• Trial of Activity for Adolescent Girls (TAAG-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions.ObjectivesThe purpose of the multicenter randomized trial was to test the effectiveness of a multicomponent school-based and community-linked intervention in preventing the decline in physical activity levels and cardiovascular fitness in middle school girls (i.e., in grades 6-8).BackgroundThe Report of the Surgeon General on Physical Activity and Health (USDHHS, 1996) emphasized that regular physical activity has important health benefits including reducing the risk of heart disease, and helping to treat and prevent high blood pressure, high cholesterol, and diabetes, and to prevent osteoporosis and colon cancer. In addition, physical activity helps control weight, reduces feelings of depression and anxiety, and promotes psychological well being. Inactivity increases with age and is more common among women than men and among those with lower income, less education, and in minorities (USDHHS, 1996). Even though adolescents are more active than adults, many do not engage in recommended levels of physical activity, and participation declines with age throughout adolescence, especially in girls (USDHHS, 1996; CDC, 1997). Fourteen percent of teenage girls get no regular exercise, twice the percentage as for boys. The proportion of adolescent girls who participate in regular vigorous physical activity declines dramatically each year they are in high school, from 61 percent among 9th graders to 41percent among 12th grade girls. In high school, enrollment for girls in daily physical education classes dropped from 41 percent in 1991 to 25 percent in 1995. Both the CDC report (1997) and the Surgeon General's Report (USDHHS, 1996) recommended the need for research testing the effectiveness of a coordinated school-based physical activity intervention linked to community agency programs to increase physical activity by adolescent girls.ParticipantsMiddle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States. Random, cross-sectional samples were drawn within schools: 6th graders in 2003 (n 1721) and 8th graders in 2005 (n 3504) and 2006 (n 3502).Researchers receiving the TAAG data are encouraged to contact study investigators that have previously published TAAG data.ConclusionsA school-based, community-linked intervention modestly improved physical activity in girls.

  Study phs004741

• NCTN: CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (E3805)

  Study ID: E3805 NCT Number: NCT00309985ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: CHAARTED: ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer Trial Description: RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen ablation therapy may stop the adrenal glands from making androgens. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether androgen-ablation therapy is more effective with or without docetaxel in treating metastatic prostate cancer. PURPOSE: This randomized phase III trial is studying androgen-ablation therapy and chemotherapy to see how well they work compared to androgen-ablation therapy alone in treating patients with metastatic prostate cancer.Data presented in the following publication(s):PMID 26244877PMID 29384722PMID 34129855Additional unpublished data from E3805Disease type(s): Reproductive System Neoplasm, Male - Prostate Cancer Dataset(s) included: NCT00309985-D1 (PMID 26244877): There are 2 datasets (NCT00309985-D1 and -D2) associated with E3805's primary publication (PMID 26244877). This dataset, NCT00309985-D1, contains baseline characteristics (e.g., age, baseline PSA value, Gleason score, etc.), stratification factors, follow-up data, progression data (e.g., post-progression treatment), dose modification information, and outcome data (overall survival, progression-free survival, PSA complete response).NCT00309985-D2 (PMID 26244877): There are 2 datasets (NCT00309985-D1 and -D2) associated with E3805's primary publication (PMID 26244877). This dataset, NCT00309985-D2, contains treatment-related toxicity data.NCT00309985-D3 (PMID 29384722): There are two datasets (NCT00309985-D3 and -D4) associated with PMID 29384722, a publication analyzing the long-term follow-up of ECOG-ACRIN trial E3805. This dataset, NCT00309985-D3, contains updated outcome data. Data that are identical to those presented in NCT00309985-D1 are not duplicated in this dataset.NCT00309985-D4 (PMID 29384722): There are two datasets (NCT00309985-D3 and -D4) associated with PMID 29384722, a publication analyzing the long-term follow-up of ECOG-ACRIN trial E3805. This dataset, NCT00309985-D4, contains data describing the reasons patients never started protocol treatment. Data that are identical to those presented in NCT00309985-D1 are not duplicated in this dataset.NCT00309985-D5 (Unpublished data): This dataset, NCT00309985-D5, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D5 contains unpublished baseline data (including prior treatments, patient characteristics and disease factors), treatment data, and PSA progression data.NCT00309985-D6 (Unpublished data): This dataset, NCT00309985-D6, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D6 contains longitudinal PSA data. NCT00309985-D7 (Unpublished data): This dataset, NCT00309985-D7, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D7 contains chemotherapy total dose data. NCT00309985-D8 (Unpublished data): This dataset, NCT00309985-D8 contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D8 contains the year of randomization for each patient. NCT00309985-D9 (Unpublished data): This dataset, NCT00309985-D9, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D9 contains more baseline data (including pathologic stage, PSA, prior treatments, etc.) and non-protocol treatment data.NCT00309985-D10 (Unpublished data): This dataset, NCT00309985-D10, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D10 contains testosterone data.NCT00309985-D11 (Unpublished data): This dataset, NCT00309985-D11, contains data collected on ECOG-ACRIN trial E3805, which are not published in the primary, long-term follow-up, or gene expression publication for the trial. NCT00309985-D11 contains fasting AM glucose and HDL data.NCT00309985-D12 (PMID 34129855): This dataset, NCT00309985-D12, contains gene expression data reported in PMID 34129855, a secondary publication of E3805 presenting transcriptional profiling associations with clinical outcomes.You are encouraged to view the PDF data dictionaries found in the "Documents" tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

  Study phs004201

• Uncovering Principles of Adaptive Regulation in Cancer Resistance Through Deep Evolutionary Profiling

  A comprehensive understanding of the emergence of therapy resistance in cancer requires new approaches capable of generating and characterizing drug resistant cell lines at scale. Here, we present the EVolution Of Lineages in Vitro (EVOLV) platform, a high-throughput approach for generating diverse libraries of viable, drug-resistant cell lines from a common progenitor. EVOLV enables deeper insights into the genomics of drug resistance as well as into the complex interplay among genomic, transcriptomic, and functional layers during cancer evolution.

  Study phs003851

• NCTN: TAILORx: Program for the Assessment of Clinical Cancer Tests: Trial Assigning Individualized Options for Treatment (PACCT-1)

  Study ID: PACCT-1NCT Number: NCT00310180Trial Title: NCTN: Program for the Assessment of Clinical Cancer Tests (PACCT-1): Trial Assigning Individualized Options for Treatment: The TAILORx TrialTrial Description:This randomized phase III trial studies the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy. You are encouraged to view the PDF data dictionaries found in the "Documents" tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication.ECOG-ACRIN Cancer Research GroupSubmitted in collaboration with the NCTN/NCORP Data ArchiveData presented in the following publication(s):PMID 29860917PMID 32271671Disease type(s): Breast Neoplasm - Breast Cancer - InvasiveAvailable Dataset(s):NCT00310180-D1 (PMID 29860917): This dataset contains the data published in the primary results publication for TAILORx (PACCT-1; NCT00310180; PMID 29860917). The dataset includes patient characteristics, OncoType Recurrence Score values, survival outcomes, and stratification variables used in the analyses presented in the publication. The data reflect the study database as of March 2, 2018. All patients who were registered to one of the arms are included.NCT00310180-D4 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D4, contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D5 contains the FACT-COG data. Dataset NCT00310180-D6 contains the FACT-G data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.NCT00310180-D5 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D5, contains the FACT-COG data. Dataset NCT00310180-D4 contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D6 contains the FACT-G data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.NCT00310180-D6 (PMID 32271671): There are three separate submissions for PMID 32271671, a publication analyzing the cognitive function among women with early breast cancer on ECOG-ACRIN trial PACCT-1. This dataset submission, NCT00310180-D6, contains the FACT-G data. Dataset NCT00310180-D4 contains additional clinical data in addition to those submitted in NCT00310180-D1 (for the trial's primary publication with PMID 29860917). Dataset NCT00310180-D5 contains the FACT-COG data. The data contained within variables identical to those presented in NCT00310180-D1 are not duplicated in this submission.Forthcoming Dataset(s): NCT00310180-D2, NCT00310180-D3

  Study phs004260

• Blood and Marrow Transplant Clinical Trials Network A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN-0702-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions.Objectives: To compare the use of tandem autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide maintenance, AHCT plus four cycles of lenalidomide, bortezomib, and dexamethasone (RVD) followed by lenalidomide, and AHCT and lenalidomide only in improving outcomes for patients with active multiple myeloma (MM).Background: At the time of this trial, initial myeloma reductive therapy followed by high-dose melphalan plus AHCT with long-term lenalidomide was the standard of care for patients newly diagnosed with MM in the United States. Despite substantive improvements in outcomes with the addition of lenalidomide, most patients still experienced disease progression and ultimately died as a result of the disease. Several approaches to further improve outcome after initial AHCT have been investigated but incremental benefit compared with maintenance therapy remains to be determined. This trial was initiated to assess whether the additional interventions of second AHCT or RVD consolidation to AHCT and lenalidomide further improve outcomes.Participants: Patients with symptomatic MM who were 70 years old or younger, had a Karnofsky score equal to or greater than 70, received at least two cycles of any regimen as initial systemic therapy without disease progression, and were within 2 to 12 months of the first dose of initial therapy were eligible.758 patients were enrolled. 247 patients were randomly assigned to the AHCT/AHCT + lenalidomide arm, 254 patients to the AHCT + RVD + lenalidomide arm, and 257 patients to the AHCT + lenalidomide arm.Design: The BMT CTN-0702 study was a Phase III multicenter trial. All patients were randomly assigned in a 1:1:1 manner at the time of enrollment, which occurred within 7 days before the first high-dose melphalan conditioning regimen. Random assignment was stratified by disease risk and transplantation center. High-risk MM was defined by presence of high β2-microglobulin, presence of cytogenetic abnormalities, or aneuploidy. Patients without cytogenetic analysis available and low β2-microglobulin level (≤5.5 mg/L) or with deletion 13 detected by fluorescence in situ hybridization were classified as standard risk.All enrolled patients were to receive high-dose melphalan (200 mg/m2) followed by mobilized autologous peripheral-blood stem-cell infusion (minimum 2 × 106 CD34+ cells/kg). Subsequent therapy was based on random assignment at the time of enrollment. The second phase of therapy started between 60 and 120 days after the first AHCT, once patients had sufficiently recovered. Patients randomly assigned to a second transplantation received high-dose melphalan (200 mg/m2) followed by autologous peripheral-blood stem-cell infusion. Patients randomly assigned to RVD consolidation received four cycles of lenalidomide 15 mg/d on days 1 to 14; bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of every 21-day cycle; and dexamethasone 40 mg per day on days 1, 8, and 15. After their initial interventions, all patients received lenalidomide starting at 10 mg per day for 3 months and increasing to 15 mg per day. Dose adjustments for toxicity were permitted. Maintenance therapy was initially designed to be given for 3 years to all patients. An amendment expanded use of lenalidomide to continue until toxicity, disease progression, or withdrawal of consent.Quality of life was assessed using the Short Form 36 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant at baseline and yearly.The primary study end point was progression free survival at 38 months.Conclusions: Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with multiple myeloma did not improve progression free survival or overall survival. Single AHCT and lenalidomide should remain as the standard approach for this population.

  Study phs004692

• NCI Cancer Model Development for the Human Cancer Model Initiative (HCMI)

  The Cancer Model Development Center (CMDC) project is part of the Human Cancer Model Initiative (HCMI) and is managed by the Office of Cancer Genomics within the Center for Cancer Genomics at the National Cancer Institute (NCI). The goal of the HCMI is to generate approximately 1000 novel human "next generation" tumor-derived models as a community resource. The models aim to faithfully recapitulate the cellular complexity and heterogeneity of human tumors. The CMDCs are tasked by the NCI with producing a proportion of the cancer models. Wellcome Sanger Institute (WSI) is a contributing member of the HCMI. Models developed by HCMI are being derived from a number of tumor types and subtypes (see below), including rare adult, pediatric and understudied cancers. The number of models and the clinical sites from which patient samples are acquired is increasing. Normal tissue, originating tumor, and tumor-derived models are sequenced. The next generation cancer models are associated with rich clinical and genomic data through the NCI Genomic Data Commons for all researchers to advance cancer research. The CMDC and HCMI models will serve as excellent tools in research to provide insight into the pathways that influence tumor growth and progression, how tumors respond to therapy, etc. Ultimately, the data generated using these models will support the development of personalized oncology. There is a delay between registered IDs and model availability. The current model count is found in The HCMI Searchable Catalog which is updated when new models are available for distribution to the research community.

  Study phs001486

• Melanoma Genome Sequencing Project

  Melanoma is the most prevalent cause of skin cancer morbidity and mortality. In order to characterize the full range of somatic mutations that may drive the growth of melanoma, we are sequencing tumor and normal DNA from a set of roughly 150 melanomas. For the majority of samples (approximately 90% of the cases), mutations in protein coding genes will be assessed in the exonic DNA of tumor-normal pairs using hybrid capture and paired-end DNA sequencing. For a few of DNA samples (approximately 10% of the cases), the entire genomes will be analyzed to assess the possible contribution of complex structural rearrangements contributing to oncogenesis. The sequencing data are supplemented by copy number profiling on the same tumors using high-density SNP arrays. Integration of these approaches will enable the unbiased and comprehensive characterization of both known and novel recurrent DNA alterations that arise in melanoma.Versions 1-4 contain whole exome and bulk RNA sequencing data for patients with melanoma.Version 5 - We compared somatic genomic profiles from matched pre-treatment and post-resistance tumor biopsies in patients with metastatic melanoma who exhibited heterogeneous responses to immune checkpoint inhibitors (ICIs). This version includes whole exome sequencing (WES) data from 14 patients.

  Study phs000452

• TIGER-LC High-Throughput Sequencing

  Intrahepatic cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We performed sequencing on multiple data levels of Thai CCA and HCC among the Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC) cohort using targeted OncoVar platform, whole exome, whole transcriptome, and whole genome metagenomic sequencing.

  Study phs001199

• Yale SPORE in Skin Cancer Project 2

  Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRab and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRab repertoire of circulating and tumor-infiltrating T cells were analyzed at the single cell level from matched tumor and blood from patients with metastatic melanoma. The data shared here consist of gene expression matrix and fastq files obtained from sequencing single-cell libraries generated with the Chromium (TM) 5' technique. For each of 18 immunotherapy naive and 11 previously treated melanoma patients, T cells (Live/CD45+/TcRab+) were FACS-sorted from PBMCs and freshly resected tumors. Metadata associated with each individual cell consist of Patient I.D., biological sex, immunotherapy status, amino acid and nucleotide CDR3 sequence of the TCR alpha and beta chain (obtained from matched VDJ region enriched libraries), and sequencing batch. Further details about previous treatment history and other clinical parameters can be found in the associated manuscripts (Lucca et al., 2021: PMID: 33651881; Lu et al., PMID: 39609626).

  Study phs002289

• Characterization of High-Grade Serous Ovarian Cancer Subtypes via Single-Cell and Spatial-Transcriptomics Profiling

  We measured gene expression in single-cell RNA sequencing samples from patients with high-grade serous ovarian cancer (HGSOC), for a study on improving HGSOC subtype definition by taking into account varying cell type proportions within tumors. The initial dataset (added October, 2020) contains 3 samples (3 individuals). The next dataset (added November, 2022) contains 34 samples from 8 individuals. The samples in the second dataset were sequenced in five different ways: 1) rRNA depletion and bulk RNA sequencing of tumor chunks, 2) rRNA depletion and bulk RNA sequencing of dissociated cells, 3) poly-A capture and bulk RNA sequencing of dissociated cells, 4) poly-A capture and scRNA sequencing of dissociated cells, 5) barcoding and pooling cells and scRNA sequencing (2 pools of 4 samples each). The third dataset (added June, 2024) contains data from one spatially resolved transcriptomics experiment (4 samples, one per Visium capture area, describing one tumor from one individual) and scRNA sequencing on 5 samples (5 individuals).

  Study phs002262

• Childhood Cancer Data Initiative (CCDI): Feasibility and Clinical Utility of Whole Genome Profiling in Pediatric and Young Adult Cancers

  Comprehensive Whole Genome Sequencing and Whole Transcriptome (RNASeq) analyses from 114 pediatric patients at Memorial Sloan Kettering. This dataset was used as a prospective clinical utility and feasibility study. By using our Isabl infrastructure for precision medicine, we developed a 2-week end-to-end pipeline to analyze cfDNA, WGS and WTS, which we refer to as cWGTS.

  Study phs002620

• Metatranscriptomic Sequencing of Biological Samples in Immunocompromised Children

  Respiratory disease in immunocompromised children can include a broad array of microbiome perturbations and infections as well as inflammation and injury to the tissue. Here we describe RNA-based next generation sequencing (mNGS) of lower respiratory samples from immunocompromised children, including those with cancer, immunodeficiencies, and a history of solid organ or stem cell transplant. We identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Lower respiratory samples largely include bronchoalveolar lavage samples with some other sample types as well. A subset of patients have paired blood and/or nasal samples also sequenced for comparative analysis.

  Study phs001684

• Single Cell RNA-Seq Reveals Malignant and Stromal Programs Associated with Metastasis in Head and Neck Cancer

  This study of head and neck cancer aimed to profile individual malignant, stromal, and immune cells in treatment-naive oral cavity squamous cell carcinoma, with or without matched metastatic cervical lymph nodes. Clinical and pathologic information was collected on all patients, in addition to a fresh biopsy sample from the primary tumor and/or metastatic lymph node at the time of initial surgery. Biopsy specimens were processed for single cell RNA-seq (scRNA-seq) and/or whole exome sequencing (WES). A total of ~6,000 single cells from 18 participants were included in the final dataset. Stromal and immune cells had consistent expression programs across patients. Conversely, malignant cells varied within and between tumors in their expression of signatures related to cell cycle, stress, hypoxia, epithelial differentiation, and partial epithelial-to-mesenchymal transition (p-EMT). One of the top scoring genes in this program was TGFβ-induced (TGFBI), implicating the classic EMT regulator TGFβ. Cells expressing the p-EMT program spatially localized to the leading edge of primary tumors. By integrating single-cell transcriptomes with bulk expression profiles for hundreds of tumors, we refined Head and Neck Squamous Cell Carcinoma (HNSCC) subtypes by their malignant and stromal composition, and established p-EMT as an independent predictor of nodal metastasis, grade, and adverse pathologic features. Our results provide insight into the HNSCC ecosystem and define stromal interactions and a p-EMT program associated with metastasis.

  Study phs001474

• Kids First and INCLUDE: Down Syndrome, Heart Defects, and Acute Lymphoblastic Leukemia

  This project is a collaboration with the trans-NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project, which seeks to improve health and quality-of-life for individuals with Down syndrome, and NHLBI's TransOmics for Precision Medicine (TOPMed) program, which seeks to apply omics technologies to improve scientific understanding of the fundamental biological processes that underlie heart, lung, blood, and sleep (HLBS) disorders. The data is also available at the INCLUDE Data Hub.Down syndrome (DS), which occurs due to trisomy 21, is one of the strongest risk factors for both congenital heart disease (CHD) and acute leukemia. For instance, children with DS have a 2000-fold increased risk of atrioventricular septal defects (AVSD) and a 20-fold increased risk of acute lymphoblastic leukemia (ALL). An important and innovative aspect of the Kids First program is understanding the overlap between structural birth defects and childhood cancer. Notably, the background of DS predisposes children to both of these phenotypes, however, the genomic architecture of risk remains largely undiscovered. In this joint Kids First/TOPMed/INCLUDE project, we are currently including >2,000 samples for whole-genome sequencing, including: 1) paired germline-tumor samples from children with DS-ALL; and 2) samples from families with DS-CHD. This work will advance our understanding of the developmental pathways that may lead to both structural birth defects and childhood cancer.The objectives of this study are to determine the genetic variants underlying AVSD and ALL risk in children with DS. Therefore, the aims of our study are: 1) compare whole-genome sequencing (WGS) data between children with documented DS-AVSD and children with DS who have structurally normal hearts to identify genetic variants that perturb heart development; and 2) compare WGS data between children with documented DS-ALL and children (from Aim 1) with DS who do not have a known history of ALL. We will also examine associations between germline mutations and somatic genomic features. This study will address the fundamental question of why children with DS have an elevated risk of AVSD and ALL. Insights into the genes that drive DS-AVSD and DS-ALL may have implications for improved genetic counseling, surveillance, clinical management, and treatment strategies for these children. Additionally, our findings may inform targeted therapies or interventions for children without DS who are at risk for structural birth defects and cancer.Additional Pediatric Cardiac Genetics Consortium (PCGC) data from children affected with Down syndrome and congenital heart disease are accessible through two separate dbGaP studies: phs001138 (Kids First) and phs001194 (TOPMed).

  Study phs002330

• Immune-Related Adverse Events after Immune Checkpoint Blockade-Based Therapy are Associated with Improved Survival in Advanced Sarcoma

  Immune activation after immune checkpoint blockade (ICB) can lead to a unique group of adverse events (AEs), which have been associated with improved outcome in many carcinomas. The association between immune-related AEs (irAEs) and outcome in patients with sarcoma is not well studied. This study has two components: (1) a retrospective clinical study of irAEs among 131 patients treated with ICB at Memorial Sloan Kettering Cancer Center and (2) an analysis of a subset of these patients who have whole transcriptome sequencing available for analysis. In the clinical study portion, we reviewed a cohort of patients with advanced sarcoma treated on prospective clinical trials utilizing ICB-based therapy between April 2017 and January 2020. The objectives were to pool the safety data from each trial, identify irAEs, and correlate them with best overall response by RECIST 1.1, progression-free survival (PFS) and overall survival (OS). Association of irAEs with response and survival was assessed using a Cox regression model. A total of 131 patients were included. Forty-two (32%) had at least one irAE of any grade and 16 (12%) had at least one Grade ≥ 3 irAE. On Cox analysis adjusting for clinical covariates that were significant in the univariate setting, the hazard ratio (HR) for an irAE (HR 0.662, 95% CI 0.421 - 1.041) approached, but did not reach statistical significance for PFS (P = 0.074), while patients had a significantly lower HR for OS (HR 0.443, 95% CI 0.246 – 0.798; P = 0.007) compared to those without or before an irAE. Tumor samples with available RNA sequencing data were stratified by presence of an irAE to identify patterns of differential gene expression. In total, 71 unique patients had RNA sequencing available for analysis. The transcriptomes of 31 of these patients have been previously uploaded to dbGaP (phs002852), leaving 36 unique transcriptomes that have not been previously publicly shared. Three patients did not agree for their sequencing to be publicly shared. Therefore, 33 unique patient samples will be uploaded to this dbGaP study. Overall, this study found that gene expression profiling on baseline tumor samples from patients who had an irAE had higher numbers of tumor-infiltrating dendritic cells, CD8+ T cells, and regulatory T cells as well as upregulation of immune and inflammatory pathways.

  Study phs003284

• Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomic Confirmatory Study of Breast, Colon, Lung, and Ovarian Tumors

  Recently, significant progress has been made in characterizing and sequencing the genomic alterations in statistically robust numbers of samples from several types of cancer. For example, The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and other similar efforts are identifying genomic alterations associated with specific cancers (e.g., copy number aberrations, rearrangements, point mutations, epigenomic changes, etc.). The availability of these multi-dimensional data to the scientific community sets the stage for the development of new molecularly targeted cancer interventions. Understanding the comprehensive functional changes in cancer proteomes arising from genomic alterations and other factors is the next logical step in the development of high-value candidate protein biomarkers. Hence, proteomics can greatly advance the understanding of molecular mechanisms of disease pathology via the analysis of changes in protein expression, their modifications and variations, as well as protein-protein interaction, signaling pathways and networks responsible for cellular functions such as apoptosis and oncogenesis. Realizing this great potential, the NCI launched the second phase of the CPTC initiative in September 2011. Renamed the Clinical Proteomic Tumor Analysis Consortium, CPTAC is beginning to leverage its analytical outputs from Phase I to define cancer proteomes on genomically-characterized biospecimens. The purpose of this integrative approach is to provide the broad scientific community with knowledge that links genotype to proteotype and ultimately phenotype. The data contained in this dataset are derived from samples designed to confirm CPTAC findings from the TCGA samples. These confirmatory samples contain breast, ovarian, colon, and lung tumors collected via a protocol optimized for proteomics. Specifically, ischemic time of the sample was controlled and restricted to less than 30 minutes. ACGT, Inc. produced whole exome, mRNAseq, and miRNAseq for these samples. Corresponding proteomic data are available at: https://cptac-data-portal.georgetown.edu/cptacPublic/ The study design was to profile colon, breast, ovarian, and lung tumors both genomically and proteomically. Germline DNA was obtained from blood. Normal control samples for proteomics varied by organ site: adjacent colon tissue for colon cases, contralateral breast tissue for some breast cases, and Fallopian tube fimbria for some ovarian cases. Lung cases had no normal control for proteomic analysis. All cancer samples were derived from primary and untreated tumors.

  Study phs000892

• A Comprehensive Genomic Study of Pediatric Malignancy

  Malignancy remains the leading cause of disease-related death in children. DNA sequencing studies have shown a paucity of actionable genomic alterations and a low mutation burden across pediatric cancers at diagnosis. We perform a comprehensive genomic and epigenomic analysis of pediatric tumor and normal tissues using next-generation sequencing to identify molecular fingerprints and targets for diagnosis, prognosis, and development of novel therapeutic methods. This study also represents one of the largest of its type to date and provides a rich genomic dataset for the pediatric cancer research community.

  Study phs001928

• Prospective Procurement of Solid Tumor Tissue to Identify Novel Therapeutic Targets

  Recent advances and insights into the molecular pathogenesis of cancer have led to the development of novel molecular and biologic targeted therapies for the treatment of advanced cancer patients. A critical challenge in extending these studies involves the identification and validation of new therapeutic targets for future cancer therapies. In this study, we performed whole exome and RNA-Seq analysis metastases to determine the nature and frequency of somatic mutations.

  Study phs001003

• Genetic Susceptibility and Biomarkers of Platinum-Related Toxicities

  The Platinum Study is an R01-funded, multicenter study of testicular cancer survivors that characterizes both long-term cisplatin-induced peripheral neuropathy (CisIPN) and cisplatin-associated ototoxicity, i.e., permanent, bilateral hearing loss. We collected data abstracted from medical records (e.g., cumulative cisplatin dose), conducted audiometric examinations, and administered self-report questionnaires, which included CisIPN symptoms.

  Study phs001621

• Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET)

  STARNET is a genetics of RNA expression study of multiple disease-relevant tissues obtained from living patients with cardiovascular disease. Tissue samples are obtained from blood, atherosclerotic-lesion-free internal mammary artery (MAM) and atherosclerotic aortic root (AOR), subcutaneous fat (SF), visceral abdominal fat (VAF), skeletal muscle (SKLM), and liver (LIV) during open thorax surgery of 600 coronary artery disease (CAD) patients. All patients gave written informed consent. The inclusion criterion was eligibility for coronary artery by-pass graft (CABG) surgery. Patients with other severe systemic diseases, such as active systemic inflammatory disease or cancer, were excluded. The primary clinical end points were the SYNTAX score based on the extent of coronary atherosclerosis assessed from preoperative angiograms. The STARNET patients are Caucasians (31% females); 32% had diabetes, 75% had hypertension, and 67% had hyperlipidemia; and 33% had an MI before age 60. By New York Heart Association criteria, 45% were class I, 42% class II, 9% class III, and 1% class IV. TYPES AND RNA SEQUENCING: 566 DNA genotype and 3577 RNA-seq profiles from seven tissues from 600 STARNET CABG patients passed quality control (on average 511 RNA-seq profiles/tissue). DNA was genotyped with the OmniExpress Exome array (Illumina, ~900k SNPs) and imputed to a total of 14,098,063 DNA variant calls (6,245,505 with minor allele frequency >5%). The STARNET subjects mainly overlap with Caucasian of Northern European (Finnish) descent. RNA sequencing was performed using the HighSeq2000 platform, poly-A (LIV, SKLM, VAF, SF and blood) and ribo-zero (AOR, MAM) protocols with 50-100 bp read lengths, single end to 15-30 million read depth.

  Study phs001203

• Pancreatic Cancer Case Control Association Study

  Pancreatic cancer is the fourth leading cause of cancer death in the United States. This is in large part due to the rapidly fatal course of this disease, as the vast majority of patients die within months of diagnosis and the five-year survival rate is less than 5. We have brought together over 8000 participants from 9 studies of pancreatic cancer, to conduct a GWAS of pancreatic cancer. The studies were drawn from the Pancreatic Cancer Case-Control consortium and include case-control studies from the United States, Europe and Australia. Sites include: Johns Hopkins National Familial Pancreas Tumor Registry, Mayo Clinic Biospecimen Resource for Pancreas Research, Ontario Pancreas Cancer Study (OPCS), Yale University, MD Anderson Case Control Study, Queensland Pancreatic Cancer Study, University of California San Francisco Molecular Epidemiology of Pancreatic Cancer Study, International Agency of Cancer Research and Memorial Sloan Kettering Cancer Center.

  Study phs000648

• Genomic Characterization of Duke Melanoma Brain Metastases

  Previous work has shown that melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biology of MBM and associations between biological features and clinical outcomes will facilitate the design of rational therapies for patients with MBM. To better characterize the molecular profile of MBM, we conducted whole exome sequencing (WES) and total RNA sequencing on MBM tissues obtained from an independent cohort of 14 patients from Duke University Medical Center. This cohort adds valuable patient samples to the field and enables strengthened investigation of somatic mutations and gene expression profiles within and between cohorts. The mutational landscape and gene expression of MBM from the Duke cohort resembled those previously reported in a previously published dataset of WES and RNA sequencing in MBM and matched ECM tissues from UT MD Anderson Cancer Center (Fischer et al., 2019 30787016). Duke MBM demonstrated similar rates of mutations in genes associated with melanoma, including BRAF, NRAS, and PTEN, as the MD Anderson cohort. Immune populations in MBM were similar between Duke and MD Anderson MBM, though Duke samples demonstrated more resting CD4+ memory T cells. The ratio of M2 to M1 macrophages in the Duke cohort was similar to that of the MD Anderson cohort. In MBM, a higher M2:M1 ratio may contribute to an immune-suppressive tumor microenvironment. Sequencing data and sample attributes from MBM tissues obtained from 14 patients from Duke University Medical Center will be available through dbGaP.

  Study phs003009

• Integrative Somatic and Germline Molecular Characterization of Genitourinary Cancers

  We have performed integrative bulk (whole exome sequencing of tumor and normal paired and whole transcriptome sequencing) and single cell analysis of primary and metastatic non-prostate genitourinary cancer specimens, such as renal and bladder tumors.Version 2: Additional sequencing of integrative bulk (whole exome sequencing of tumor and normal paired and whole transcriptome sequencing) and single cell analysis of primary and metastatic non-prostate genitourinary cancer specimens. Within this version, we include a cohort to study muscle-invasive bladder cancer (MIBC). We hypothesized that specific interactions between specific urothelial malignant cells and immune cells jointly promote chemotherapy resistance in MIBC. To investigate this hypothesis, we paired complementary single-nucleus RNA sequencing (snRNAseq) and spatial transcriptomic methods in clinically integrated contexts with focused functional assessments to understand cancer and immune cell multicellular communities implicated in resistance to neoadjuvant cisplatin-based chemotherapy.

  Study phs002065

• Genomic Profiling of Melanoma

  This study reports on genomic profiling [whole-exome sequencing (WXS), bulk RNA sequencing (RNA-seq), and/or single-cell RNA sequencing (scRNA-seq)] of patient-derived melanoma samples and matched normal samples. The goal is to elucidate the genetic and cellular basis of sun-exposed and sun-shielded melanomas and to relate these findings to survival and regional metastasis. Specimens were collected by the Tissue Resource Core of the Yale SPORE in Skin Cancer with participants' informed signed consent according to Health Insurance Portability and Accountability Act (HIPAA) regulations with a Human Investigative Committee protocol. The melanomas used for sequencing were from fresh or snap-frozen tumors, or from short-term cell cultures. The cell cultures were routinely checked for mycoplasma contamination and were discarded when found positive. Matching normal DNA was from circulating lymphocytes or normal skin. We also include 77 WES-sequenced samples from the Yale Spitzoid neoplasm repository, which collects specimen and data according to a protocol approved by the Yale Human Investigative Committee.

  Study phs000933

• Germline Genetics of Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

  Myelodysplastic syndromes (MDS) are part of a heterogeneous and overlapping group of clonal diseases that arise in the hematopoietic stem or progenitor cells and also include acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and the hybrid MDS/MPN entities. Individuals with MDS have a high risk of progressing to leukemia, with approximately 30% expected to develop AML. This study evaluates genetic susceptibility to myeloid malignancy using data from population-based case control studies of myelodysplastic syndromes and acute myeloid leukemia in adults (ages 18-85 years) and pediatric MDS cases with banked samples at the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult cases were identified through the Minnesota Cancer Reporting System and controls were recruited from the State Driver's License/Identification Card list. DNA samples were collected via mouthwash collection kits (AML cases and controls) or Oragene saliva collection kits (adult MDS cases and controls). Pediatric MDS samples were banked at CIBMTR prior to receipt of a transplant and DNA was extracted from isolated T cells or whole blood samples. Genotyping data were generated using the Illumina Global Diversity array and quality control and genotype calling was conducted using established best practices. Our primary analyses investigated the contribution of genetic variation to MDS risk and evaluated the role of the killer cell immunoglobulin receptors (KIR) on incidence and survival.

  Study phs002962

• CIDR: Molecular Pathological Epidemiology of Colorectal Cancer

  Colorectal cancer, the second most commonly diagnosed cancer is a biologically heterogeneous disease. To characterize the molecular attributes of colorectal tumors, we conducted targeted sequencing at the Center for Inherited Disease Research (CIDR) on 4,518 tumor and matched normal DNA samples from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR). These consortia are based on cohort and population-based case-control studies.

  Study phs001905

• Genetic Analysis of Skin Cells

  Cutaneous squamous cell carcinoma (cSCC) is a form of skin cancer originating from keratinocytes in the skin. They have high mutation burdens, primarily driven by UV-radiation-induced DNA damage. The order in which mutations undergo selection during the evolution of cSCC is not known. A subset of cSCCs grow out of benign neoplasms called actinic keratoses. To better understand the evolution of cSCC, we identified cases of cSCCs adjacent to actinic keratoses. From these cases, we separately microdissected the surrounding normal skin, the actinic keratosis, and the cSCC, and we performed targeted DNA-sequencing on the tissue from each area. We reconstructed tumor phylogenies and performed spatial transcriptomics on the 10X FFPE Visium platform on a subset of cases. Collectively, these studies revealed the mutational and gene expression changes that arise during the evolution of cSCC.

  Study phs003282

• Genomic Sequencing of Pediatric Rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood accounting for approximately 350 newly diagnosed cases yearly in the United States. With the development of multimodal chemotherapy regimens, relapse-free survival rates have improved to 70-80% in patients with localized disease albeit with significant toxicity. Unfortunately, despite aggressive treatment, patients with metastatic or recurrent disease continue to suffer from high mortality. Further characterization of the genetic events underlying this tumor type is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. In a collaborative effort between the National Cancer Institute, the Children's Oncology Group, and the Broad Institute, we use a combination of whole-genome and whole-exome sequencing to characterize the landscape of somatic alterations in 147 tumor/normal pairs.

  Study phs000720

• Single-Cell Genomic Analysis of Gastrointestinal Cancer

  Our study aimed to define the heterogeneity of gastrointestinal cancers at a single-cell resolution. We subjected single-cell suspensions derived from surgical resections of gastrointestinal cancer tissue, paired normal tissue, peripheral blood mononuclear cells (PBMCs) or their ex vivo cultures to high-throughput microfluidics based single-cell RNA and DNA sequencing. We analyzed the features of the tumor microenvironment including fibroblasts, endothelial cells, macrophages and lymphocytes to determine their contribution to tumor growth and progression. We also characterized the mechanisms of immunosuppression in these tumors. This analysis led to novel insights into the biology of the microenvironment and also enabled the identification of new treatment targets.

  Study phs001818

• Genomic Changes in Breast Cancer Among Chinese Women in Hong Kong

  Recently, tumor sequencing and profiling analyses have improved molecular classification and refined existing breast cancer subtypes. However, epidemiologic data are absent in most somatic profiling studies even in extensively studied Western populations. The expansion of genomic studies to understudied populations with the integration of etiologic factors will allow the capture of a much wider range of genetic structure and mutagenic exposures associated with breast cancer risk. We therefore conducted a detailed molecular characterization of paired breast tumor/normal tissues using fresh frozen tissues collected from breast cancer cases in an ongoing breast cancer case-control study in Hong Kong. These analyses included whole genome (WGS)/exome sequencing (WES), targeted DNA panel sequencing, RNA sequencing (RNA-Seq), and genome-wide methylation profiling analyses.

  Study phs001870