6048 results for "canc*"

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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• 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.

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