Search Results - EGA European Genome-phenome Archive

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

6048 results for "canc*"

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