3288 results for "ovarian cancer"

in 28.68 milliseconds.

• CTCF/cohesin-binding sites are frequently mutated in cancer

  Cohesin is present in almost all active enhancer regions, where it is associated with transcription factors. Cohesin frequently colocalizes with CTCF (CCCTC-binding factor), affecting genomic stability, expression and epigenetic homeostasis. Cohesin subunits are mutated in cancer, but CTCF/cohesin-binding sites (CBSs) in DNA have not been examined for mutations. Here we report frequent mutations at CBSs in cancers displaying a mutational signature where mutations in A•T base pairs predominate. Integration of whole-genome sequencing data from 213 colorectal cancer (CRC) samples and chromatin immunoprecipitation sequencing (ChIP-exo) data identified frequent point mutations at CBSs. In contrast, CRCs showing an ultramutator phenotype caused by defects in the exonuclease domain of DNA polymerase ɛ (POLE) displayed significantly fewer mutations at and adjacent to CBSs. Analysis of public data showed that multiple cancer types accumulate CBS mutations. CBSs are a major mutational hotspot in the noncoding cancer genome.

  Study EGAS00001003010

• Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients.

  Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.

  Study EGAS00001007582

• Resolving the immune landscape of human prostate at a single cell level in health and cancer

  The prostate gland produces prostatic fluid, high in zinc and citrate and essential for the maintenance of spermatozoa. Prostate cancer is a common condition with limited treatment efficacy in castration-resistant metastatic disease, including with immune checkpoint inhibitors. We used single-cell RNA-sequencing to perform an unbiased assessment of the cellular landscape of human prostate and identified a previously unappreciated subset of tumour-enriched androgen receptor-negative luminal epithelial cells, with increased expression of cancer-associated genes. We also found a variety of innate and adaptive immune cells in normal prostate that were transcriptionally perturbed in prostate cancer. An exception was a unique, prostate-specific, zinc transporter-expressing macrophage population (MAC-MT), that contributed to tissue zinc accumulation in homeostasis, but showed enhanced inflammatory gene expression in tumours, including T cell-recruiting chemokines. Remarkably, enrichment of the MAC-MT signature in cancer biopsies was associated with improved disease-free survival, suggesting beneficial anti-tumour functions.

  Study EGAS00001005787

• genome-wide cfDNA methylation analysis

  To characterise cfDNA methylome in metastatic prostate cancer

  Study EGAS00001003958

• Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

  Study EGAS00001007477

• Whole genome sequencing data using Adaptive sampling from 33 patients with hereditary cancer syndrome

  We performed whole genome sequencing using adaptive sampling with GridION on 33 patients with clinically suspected hereditary cancer syndromes to evaluate an efficient computational workflow.

  Study JGAS000654

• Target sequencing of ROS1-rearranged lung cancer patients

  We performed target capture sequencing of ROS1-rearranged non-small cell lung cancer patients to develop and examine the efficacy of new molecular targeted drug against ROS1 tyrosine kinase.

  Study JGAS000189

• S_CORT_Stratification_in_COloRecTal_cancer_

  Colorectal cancer samples will be submitted for Illumina sequencing using a custom capture of 116 genes implicated in colorectal tumourigenesis. Driver mutations will be detected and ultimately correlated with phenotypic data.

  Study EGAS00001001521

• ChIP_sequencing_in_Cancer_Cell_Lines

  The project is to evaluate the genomic binding sites of the histone demethylase JARID1C. This gene was recently identified in CGP as a novel recessive cancer gene in human renal cell carcinoma.

  Study EGAS00001000203

• BIG_MS_Pilot

  Testing logistics and infrastructure of molecular screening program. Core biopsies taken from invasive recurrent or metastatic breast cancer to evaluate and identify molecular traits rendering them suitable for clinical trials

  Study EGAS00001000616

• Targeted_gene_fusion_sequencing__Fus_seq__in_mesothelioma

  This is a small pilot data set to test the feasibility of cDNA exomes across 1200 cancer cell line panel. cDNA exomes or Fus-seq is further explained in this studies Abstract.

  Study EGAS00001000390

• Probabilistic modeling of personalized drug combinations from integrated chemical screen and molecular data in sarcoma

  Background: Cancer patients with advanced disease exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient’s epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient’s primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. Results Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). Conclusions These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

  Study EGAS00001003564

• Investigation of MMBIR DNA Repair in Normal and Cancer Human Cells

  Microhomology-mediated break-induced replication (MMBIR) is a DNA repair pathway in which template switching at microhomology was proposed to promote complex genomic rearrangements (CGRs) that contribute to cancer. Yet, the extent of MMBIR activity in genomes is poorly understood due to difficulty in directly identifying MMBIR events by whole genome sequencing (WGS). This study aims to detect MMBIR events in human cancer genomes and to determine their frequency and complexity in tumors as compared to their non-tumor counterparts. This study contains WGS data from matched tumor and normal samples, and cultured cell line control WGS datasets that are not currently represented in other cancer genome databases.

  Study phs002237

• Division of Cancer Epidemiology and Genetics (DCEG) Imputation Reference Dataset

  We have built a new resource for imputation of SNPs for existing and future genome-wide association studies (GWAS), known as the Division of Cancer Epidemiology and Genetics (DCEG) Reference Set. The first build of the data set includes 728 cancer-free individuals of European descent from three large prospectively sampled studies, 98 African-American individuals from the Prostate, Lung, Colon, and Ovary Cancer Screening Trial (PLCO), 74 Chinese individuals from a Chinese clinical trial in Shanxi, China (SHNX), and 349 unrelated individuals from the HapMap Project (see Molecular Data Section for details on arrays used). The final harmonized dataset includes 2.8 million autosomal polymorphic SNPs on 1,249 subjects after rigorous quality control metrics were applied.

  Study phs000396

• Gastric_Mutational_Signatures__GMS_

  This study aims to characterise the mutation burdens and signatures of adult stem cells derived from different regions of the stomach in order to gain insight into the causes and preclinical evolution of the diverse cancer subtypes. Clonal populations of cells from different anatomical locations of the stomach will be derived through organoid culture and/or laser microdissection and interrogated by whole genome sequencing and/or targeted pulldown. A total of circa 300 samples from 20 – 30 donors (cancer and non-cancer patients undergoing total/partial gastrectomy) will be analysed for mutational burden and signatures and genomic findings correlated with topology, age, risk factors and different stages of pre-neoplastic or neoplastic progression.

  Study EGAS00001002938

• Gastric_Mutational_Signatures__GMS_

  This study aims to characterise the mutation burdens and signatures of adult stem cells derived from different regions of the stomach in order to gain insight into the causes and preclinical evolution of the diverse cancer subtypes. Clonal populations of cells from different anatomical locations of the stomach will be derived through organoid culture and/or laser microdissection and interrogated by whole genome sequencing and/or targeted pulldown. A total of circa 300 samples from 20 – 30 donors (cancer and non-cancer patients undergoing total/partial gastrectomy) will be analysed for mutational burden and signatures and genomic findings correlated with topology, age, risk factors and different stages of pre-neoplastic or neoplastic progression.

  Study EGAS00001002939

• Subtype-associated epigenomic landscape and 3D genome structure in bladder cancer

  We determine the genome-wide transcriptome, enhancer landscape and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration.

  Study EGAS00001005071

• Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer

  Study EGAS00001007291

• WGS

  Whole-genome sequencing of pancreatic cancer organoids and matched germline controls.

  Study EGAS00001007211

• Anonymized germline variants of prospectively characterized clinical cancer specimens

  These clinical specimens represent solid tumors and matched blood controls that were collected as part of patients' routine care at Memorial Sloan Kettering Cancer Center. They were sequenced on the targeted platform MSK-IMPACT. Here, we performed germline variant calling on the normal blood specimens and assessed their zygosity in the concomitant tumor specimens for comprehensive exploration of the landscape of pathogenic germline variants in patients with advanced cancer.

  Study phs001858

• Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) - germline whole genome sequencing

  This study consists of whole genome sequencing (target: average 30x coverage) of 110 European-ancestry (EA), early-onset, family-history-positive breast cancer cases, 21 Asian cases, 25 African-American cases, and 24 controls from six studies participating in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) consortium, part of the NCI's Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative ( http://epi.grants.cancer.gov/gameon/ )

  Study phs001483

• Meta-Analysis of Genome-Wide Association Studies of Bladder Cancer Risk

  This meta-analysis consists of genome-wide genotype for 13,447 cases and 342,580 controls of European ancestry to identify novel susceptibility loci for bladder cancer. Cases were defined as histologically confirmed primary carcinoma of the urinary bladder of all stages, including carcinoma in situ (International Classification of Diseases for Oncology, C670-C679, 188). All histologic subtypes were included. Summary-level results for the association between genotyped/imputed variants and risk of bladder cancer are included.

  Study phs003342

• Matched_breast_cancer_fusion_gene_study

  Genomic libraries (500 bps) will be generated from total genomic DNA derived from 40 breast cancer samples and subjected to total of eight lanes of 37 bp, paired end sequencing on the llumina GA. Paired reads will be mapped to build 37 of the human reference genome to facilitate the generation of genome wide copy number information, and the identification of novel rearranged cancer genes and gene fusions.

  Study EGAS00001000031

• Understanding Determinants of Racial Disparities in Lung Cancer Incidence

  This is a nested case-control study designed to evaluate the association between common genetic variants and the risk of lung cancer. The study included 1258 cases and 1252 controls selected from the Southern Community Cohort Study (SCCS), a large, prospective observational cohort. Cases were identified from cancer registries across the catchment area of the SCCS. Cases and controls were frequency matched on age, sex, race, and enrollment site (community health center vs general population).

  Study phs003789

• Whole-exome sequencing profiling of patients with metastatic prostate cancer at VHIO

  Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and a RAD51 immunofluorescence (RAD51-IF) iprimary or metastatic biopsies from patients with stage IV prostate cancer. Whole-exome sequencing was pursued for paired tumor-normal samples.

  Study EGAS50000000736

• MOSAIC - Multi-Omics Spatial Atlas In Cancer

  MOSAIC is a collaborative initiative founded by Owkin, Lausanne University Hospital (CHUV), Charité Universitätsmedizin Berlin, University Hospital Erlangen (UKER), Gustave Roussy Institute in Paris, and University of Pittsburgh. The goal of MOSAIC is to build the largest collection of spatial omics data in cancer. By integrating comprehensive high quality clinical annotations with advanced deep profiling techniques, MOSAIC aims to uncover novel cancer subtypes and identify key drug targets and biomarkers within them.

  Study EGAS50000000689

• Development of blood-based biomarkers for precision medicine in castration-resistant prostate cancer

  Cell-free DNA (cfDNA) testing is emerging as a tool for cancer precision medicine. However, little is known about the clinical significance of low-frequency variants detected in circulating cell-free tumor DNA (ctDNA) from castration-resistant prostate cancer (CRPC) patients. We conducted targeted sequencing of cfDNA and paired leukocyte DNA from CRPC patients using molecular barcodes, and ctDNA variants with a variant allele frequency ??? 0.1% were detected using an in-house pipeline.

  Study JGAS000330

• Genome- and epigenome-driven evolutionary dynamics of tumour-immune coevolution within primary colorectal cancers

  This data includes targeting sequencing of the immunopeptidome from 94 samples, usually individual laser microdissected cancer glands, from 11 cases of colorectal cancer. The data were used to test for evidence of immunoediting (antigen depletion) in colorectal cancers. The full data description is provided in the original manuscript https://pmc.ncbi.nlm.nih.gov/articles/PMC10888923/. The 11 colorectal cancers had been previously multiomic profiled with data described in the parts of this disposition.

  Study EGAS50000001154

• Breast Cancer - immune clusters - RNA-seq

  In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer. Immune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features. We also found the immune clusters associated with treatment response. Further using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.

  Study EGAS00001003631

• Targeted sequencing of paired tumour/blood of 34 T1 stage bladder cancer patients

  Stage T1 bladder cancer presents a high risk of progression and requires improved understanding. In continuation of our whole-exome sequencing study on this subtype of the disease, we carried out this targeted paired tumour/blood sequencing study including 34 T1 stage bladder cancer patients. Agilent’s SureDesign tool was used to design a 1.133 Mb SureSelect custom capture for all coding exons of the 140 selected candidate genes.

  Study EGAS00001005767

• Dual-mTOR inhibitor Rapalink-1 reduces prostate cancer patient-derived xenograft growth and alters tumor heterogeneity

  Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.

  Study EGAS00001004431

• RRBS data from TRACERx non-small cell lung cancer (NSCLC) tumours and matched normal adjacent tissue.

  TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at multi-region RRBS data from the TRACERx cohort selected for quantity of material available and high tumour purity

  Study EGAS00001006523

• The Landscape of N-6 Methyladenosine in Primary Localized Prostate Cancer

  Using meRIP-sequencing, we profiled N-6 methyladenosine (m6A) in a cohort of 148 primary prostate cancer samples as part of the Canadian Prostate Cancer Genome Network project (CPC-GENE). Paired-end sequencing of 150 bp reads were mapped to GRCh38.p13 using annotations from gencode.v34.chr_patch_hapl_scaff.annotation.gtf. Peaks were called using MeTPeak, joint peaks were identified and IP reads were quantitated, normalized and adjusted using Input reads to obtain estimates of m6A abundance.

  Study EGAS00001006925

• Epithelioid haemangioendothelioma (EHE) case series from the Stafford Fox Rare Cancer Program

  Nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program were collated via nation-wide referral to the Australian Rare Cancer Portal. Molecular analysis of RNA, DNA or both was possible in seven of nine cases. Survival was highly variable and unrelated to molecular profile. DNA sequences for two cases are deposited here.

  Study EGAS00001007474

• PE-CGS: Optimizing Engagement of Hispanic Colorectal Cancer Patients in Cancer Genomic Characterization Studies

  Colorectal Cancer (CRC) is the second leading cause of cancer death in the US. Hispanic/Latinos (H/L) are the largest and fasting growing ethnic group in the US, and cancer is the leading cause of death among H/L in the US. Therefore, we need to fully understand the full complexity of the molecular etiology of cancer in this ethnic group. For instance, although incidence rates of CRC are lower among Latinos as compared to Whites or African Americans, Hispanics with metastatic disease have shorter overall survival when adjusted for health care setting, demographics, disease characteristics and treatment factors. H/L also tend to be diagnosed at a younger age and with higher stage, and we have previously reported that Mexican H/L in California have the greatest proportion of young (The Cancer Genome Atlas has provided a deep overview of the molecular taxonomy of CRC in 594 cases, however, less than 1% of the cases (n=5) were H/L. Therefore, it is imperative for us to take more detailed assessment of the molecular genomic landscape of CRC in H/L. One of the major issues likely limiting our ability to perform these large genomic initiatives in minority patients is that Patient or Participant Engagement practices may not be investigated to identify best practices for accruing and consenting patients into clinical translational biomedical research studies. This concept of Participant Engagement is critically important for both the patients and the translational cancer research community. Optimizing and improving our approaches for directly engaging patients at initial contact, throughout the course of a translational genomic study, and during the time of return of results is likely to lead to stronger relationships between the medical community and patients, but could also lead to significant improvement in outcomes for patients and for the cancer care community as a whole. As such, we propose the creation of the USC Center for Optimization of Participant Engagement in Cancer Characterization (COPECC) with a focus on optimizing the engagement of Latinos in CRC Genomic Characterization research studies. USC COPECC would serve as a member of the NCI U2C Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Our investigative team includes experts in all relevant areas of research for genomic characterization, participant engagement, and engagement optimization. We have an established platform for consenting patients into cancer genomics studies that will serve as a standard process. The overall goal of USC COPECC is to generate results on participant engagement optimization and CRC genomic research that will be shared with the broader community to distribute best practices for engaging Latinos in hopes of improving overall outcomes for CRC in this underserved population.

  Study phs003985

• cell-Free DNA Genomic Profiling and its Clinical Implementation in Advanced Prostate Cancer

  Sixty-eight patients with advanced prostate cancer in castration-resistant or castration-sensitive settings undergoing treatment at the University Hospital Basel or the St. Claraspital Basel (Switzerland) were selected for targeted parallel sequencing analysis on liquid biopsy (plasma cfDNA) and matched formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples.

  Study EGAS50000000234

• RNA Sequence-Based Analysis Used to Compare Breast Primary and Metastatic Tumor Pairs

  The goal of this study is to capture the transcriptome landscape of luminal and basal-like metastatic breast tumors. We will aim to show the importance of using the most up-to-date cancer biopsy for detecting cancer drivers that were often not present in the primary tumor.

  Study phs001866

• Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer

  Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC).

  Study EGAS50000000775

• Angiopredict: predicting response for bevacizumab treatment

  In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers worked with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to bevacizumab containing therapy. In this retrospective study, copy number profiles were determined using whole genome shallow sequencing, and progression free survival and treatment data was collected.

  Study EGAS00001002724

• Somatic_mutation_and_clonal_evolution_in_the_human_bladder_WES_NOVASEQ

  n this study, we aim to characterise the landscape of mutation and clonal selection in the human bladder. The study includes targeted sequencing of laser-dissected microbiopsies from the bladder. The samples utilised in this study will include urothelium from transplant donors with no history of bladder cancer and cystectomy specimens from patients with bladder cancer.

  Study EGAS00001003456

• Multi-region RNA sequencing of tumour regions and tumour-adjacent normal lung tissue

  TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC).

  Study EGAS00001006517

• Tracing early predictors of glioma evolution under therapy

  Clonal evolution drives cancer progression and therapeutic resistance. Recent studies revealed divergent longitudinal trajectories in gliomas, but early molecular traits steering post-treatment cancer evolution remain unclear. We analyzed sequencing data of 544 initial-recurrent adult diffuse glioma pairs to identify genomic and transcriptomic early predictors of tumor evolution in each molecular subtype.

  Study EGAS00001006894

• Genomic characterization of metastatic breast cancers

  While large efforts have been done to characterize early breast cancer, little is known about the genomic landscape of metastatic breast cancer. In the present study, we performed whole exome sequencing of 629 metastatic breast cancers, in order to identify new candidate targets and better stratify patients eligible for innovative therapies.

  Study EGAS00001003290

• Circulating tumor DNA, pathological and immunologic responses to neoadjuvant nivolumab or nivolumab plus relatlimab and chemoradiotherapy in resectable esophageal/gastroesophageal junction cancer

  Study EGAS00001007299

• National Human Genome Research Institute Tumor Sequencing Project (TSP) - Lung Adenocarcinoma

  The Tumor Sequencing Project (TSP) Consortium is a collaboration among participants at the Baylor College of Medicine Human Genome Sequencing Center, the Broad Institute Genome Sequencing Platform, the Dana Farber Cancer Institute, the Memorial Sloan-Kettering Cancer Center, the Genome Sequencing Center and Siteman Cancer Center at Washington University, the M.D. Anderson Cancer Center and the University of Michigan Medical Center. The TSP Part A will pilot approaches to large-scale identification of genomic changes in tumors by sequencing the exonic regions of 623 genes in 188 specimens of adenocarcinoma of the lung, as well as using high density SNP genotyping arrays for high resolution identification of changes in chromosomal copy number. The TSP Part B will pilot approaches to tumor characterization of lung adenocarcinoma samples using next-generation sequencing technologies and benchmark those results against Part A data generated with ABI3730 instruments.

  Study phs000144

• Glioma International Case Control Study (GICC)

  The main goals of the GICC Study were: 1) to identify novel genetic risk variants for glioma, as well as validate variants implicated by previous genome-wide association studies of glioma; and 2) to explore biologically relevant gene-gene and gene-environment interactions in glioma susceptibility. The GICC Study includes participants from the following centers: Brigham and Women's Hospital (Boston, Massachusetts), Case Western Reserve University (Cleveland, Ohio), Columbia University (New York, New York), the Danish Cancer Society Research Centre (Copenhagen, Denmark), Duke University (Durham, North Carolina), the University of Texas MD Anderson Cancer Center (Houston, Texas), Memorial Sloan Kettering Cancer Center (New York, New York), the Mayo Clinic (Rochester, Minnesota), NorthShore HealthSystem (Chicago, Illinois), Umea University (Umea, Sweden), the University of California, San Francisco (San Francisco, California), the University of Southern California (Los Angeles, California), and the Institute of Cancer Research (London, United Kingdom).

  Study phs001319

• Methylation Profiles of Cell-Free DNA Using Nanopore Sequencing

  Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based single-molecule sequencing to measure cfDNA methylomes. This approach generated up to hundreds of millions of reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.Control subjects consist of healthy individuals without a positive diagnosis of cancer. cfDNA was obtained through purification of plasma from blood draws. Genomic DNA (gDNA) was derived from extraction of primary tumor tissue or from leukocytes from blood draws.

  Study phs002950

• Transfer Learning Associates CAFs with EMT and Inflammation in Tumor Cells in Human Tumors and Organoid Co-Culture in Pancreatic Ductal Adenocarcinoma

  This study examined the transcriptional changes induced by cancer associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma patient-derived tumor organoids. We hypothesized that cancer associated fibroblasts impacted tumor cell transcription to promote tumorigenic behavior. Using patient-matched cells from 3 patients, we compared the transcriptional profiles of patient-derived organoids in monoculture to patient-derived organoids co-cultured with CAFs. Similarly, we looked at the transcriptional changes in matched patient-derived cancer associated fibroblasts grown in monoculture or co-cultured with patient-derived organoids. With a focus on intercellular crosstalk, we identified crosstalk between cancer associated fibroblasts and patient-derived organoids through VEGFA and NRP1. This was identified by bulk RNA sequencing and examined dynamically in organoid-CAF co-culture. This dbGaP deposit is the bulk RNA sequencing data for these 3 patients.

  Study phs003563

• Cancer and germline exomes consisting of FASTQ paired-end reads from melanoma and lung cancer samples

  Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

  Study EGAS00001003723

• Human breast transcriptome analysis

  Obesity is a risk factor for the development of post-menopausal breast cancer and is associated with a worse breast cancer prognosis. Here we carried out transcriptome profiling on nontumorous breast tissue to define the molecular changes that occur related to excess body fat and adipose inflammation. A second goal was to determine if blood biomarkers reflect molecular changes in the breast. Increases in a variety of pathways linked to tumor development and progression were found. Moreover, increased expression of several drug targets including aromatase, the rate-limiting enzyme for estrogen biosynthesis, and PD-1 was observed. Various blood biomarkers that are associated with either elevated risk of breast cancer or worse prognosis were altered and correlated with molecular changes in the breast. Collectively, this study helps to explain both the link between obesity and breast cancer and the utility of blood biomarkers for determining risk and prognosis.

  Study EGAS00001004665