Search Results - EGA European Genome-Phenome Archive

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

Proteogenomic Characterization of Human Uterine Cervical Cancer

We report a proteogenomic analysis of human cervical cancer. Mutation-phosphorylation correlations revealed associations of proliferation and invasion-related signaling pathways with somatic mutations in significantly mutated genes. mRNA-protein abundance correlations identified molecules with tumor promoting or suppressing functions correlating with patient survival. Integrated clustering of mRNA, protein, and phosphorylation data provided six subtypes (Sub1-6) of cervical cancer. Compared with the previous subtypes identified from transcriptome data, protein data further identified subgroups of squamous carcinoma and adenocarcinoma based on stromal and immune characteristics. In the squamous subgroups, Sub4 showed higher T-cell immunity than Sub5, and myeloid-derived suppressive immune cells that inhibit T-cell proliferation were enriched in Sub5. In the adeno subtypes, Sub3 had higher myofibroblasts that modulate anti-tumor immunity than Sub6. These stromal and immune features were consistent with the survival patterns of patients in the subtypes. Our proteogenomic analysis provides patient stratification and therapeutic targets in cervical cancer and improves our understanding of cancer biology.

Study phs002916

NCTN: A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men with Prostate Cancer Metastatic to Bone (CALGB-90202)

Study ID: CALGB-90202NCT Number: NCT00079001Alliance for Clinical Trials in OncologySubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men with Prostate Cancer Metastatic to Bone (CALGB-90202)Trial Description:RATIONALE: Zoledronate may prevent or decrease skeletal (bone)-related events (such as pain or fractures) caused by bone metastases and androgen deprivation therapy. It is not yet known whether treatment with zoledronate is effective in preventing bone-related events in patients who have prostate cancer and bone metastases.PURPOSE: This randomized phase III trial is studying how well zoledronate works in preventing bone-related events in patients who are receiving androgen deprivation therapy for prostate cancer and bone metastases. Clinical data presented in the following publication(s):PMID 24590644Additional unpublished data from CALGB-90202Disease type(s): Reproductive System Neoplasm, Male - Prostate CancerClinical dataset(s) included:NCT00079001-D1 (PMID 24590644): NCT00079001-D1 is one of 3 datasets that contain the data published in the analyses of PubMed ID 24590644 (-D1 through -D3). This dataset contains baseline characteristics, stratification factors, prior therapy, and metastatic site data.NCT00079001-D2 (PMID 24590644): NCT00079001-D2 is one of 3 datasets that contain the data published in the analyses of PubMed ID 24590644 (-D1 through -D3). This dataset contains primary analysis (time to skeletal-related event), time-to-event analysis, and treatment discontinuation data.NCT00079001-D3 (PMID 24590644): NCT00079001-D3 is one of 3 datasets that contain the data published in the analyses of PubMed ID 24590644 (-D1 through -D3). This dataset contains the toxicity data reported.NCT00079001-D4 (Unpublished data): Dataset NCT00079001-D4 contains data collected on Alliance trial CALGB-90202 which are not published in the primary publication for the trial. NCT00079001-D4 includes data on type of progression, time to progression, cause of death and clinical follow-up data.You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004392

Environmental Chemical Body Burden and Prospective Breast Cancer Risk in the Cancer Prevention Study-3 Cohort - CIDR

This study is focused on chemical body burden of per- and poly-fluoroalkyl substances (PFAS), and concomitant risk of developing invasive breast cancer during the menopausal transition. We hypothesized that elevated body-burden levels of these endocrine-disrupting chemicals (EDCs) will increase the risk of developing breast cancer, and that alterations of the methylome will link these chemical exposures and breast cancer. In Specific Aim 1, using samples and data from a prospective study of women in the American Cancer Society (ACS) Cancer Prevention Study 3 (CPS-3), we are assessing the association between body burden of PFAS during the menopausal transition and subsequent development of invasive breast cancer. The California Environmental Chemistry lab is determining PFAS levels in plasma samples collected 1 to 7 years prior to a diagnosis of invasive breast cancer from 998 ACS CPS-3 participants and 998 matched, cancer-free CPS-3 participants. All subjects were between 40 and 57 years of age when the blood sample was taken. In Specific Aim 2, studying the same participants, DNA methylation (DNAm) using Infinium MethylationEPIC BeadChips was conducted at Center for Inherited Disease Research (CIDR). We are conducting an epigenome-wide association study (EWAS) to identify DNAm changes associated with levels of PFAS in the cancer-free participants. We then will determine the association between the PFAS-associated DNAm changes and risk of developing breast cancer. The design is a nested case control study within the ACS CPS-3 cohort. Available data include the DNAm data and phenotypic data on case or control status, age at diagnosis of breast cancer, age at blood draw for cases and controls, and self-reported race/ethnicity.

Study phs003494

APOLLO-BRCA-1: Proteogenomic Analysis of Invasive Breast Tumors in Young (less than 40 years old) vs Older Patients (greater than or equal to 60 years old)

Breast cancer in women under the age of 40, accounting for ~5% of breast cancer diagnosed in the U.S., is more aggressive with worse outcomes than breast cancer in older women. The aim of this study is to to identify molecular features that may underlie the worse outcomes in young women with breast cancer. We performed a first-ever integrated proteogenomic study from a matched cohort of laser-microdissected tumors of 34 young (age Proteomic Data Commons at the National Cancer Institute.

Study phs003636

Childhood Cancer Data Initiative (CCDI): Metastatic Osteosarcoma snMultiome Profiling

Metastatic osteosarcoma is an aggressive bone malignancy affecting pediatric, adolescent, and young adults. While recent research has increasingly focused on understanding the complex biology of the osteosarcoma microenvironment, the tumor vasculature is understudied, especially in the context of metastatic disease. To address this, we performed single-nuclei multi-ome (RNA+ATAC) sequencing on a cohort of 24 human metastatic osteosarcoma specimens. Our data shows that endothelial cells universally exhibit a hybrid endothelial–mesenchymal state consistent with endothelial-to-mesenchymal transition (EndMT). Additionally, we uncovered that a subset of diploid endothelial cells adopts an osteoblastic cell fate as evidenced by gene expression and gene regulatory network (GRN) analysis. Joint copy-number analysis of our dataset identified a subset of osteosarcoma cells with endothelial transcriptional programs and GRNs, indicative of vascular mimicry. In vitro assays and in vivo lineage tracing experiments using syngeneic murine models validated both vascular mimicry and endothelial to-osteoblastic transdifferentiation. Collectively, these findings highlight the remarkable plasticity and lineage infidelity of both endothelial and osteosarcoma cells in patient specimens and a metastatic syngeneic murine model, provide novel insights into the functional role of endothelial cells in the metastatic osteosarcoma microenvironment, and challenge current understanding of osteosarcoma biology.

Study phs004490

NCTN: A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma (RTOG-1010)

Study ID: RTOG-1010NCT Number: NCT01196390 NRG OncologySubmitted in collaboration with the NCTN/NCORP Data ArchiveTrial Title: NCTN: A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma (RTOG-1010)Trial Description: This randomized phase III trial studies how well radiation therapy, paclitaxel, and carboplatin with or without trastuzumab work in treating patients with esophageal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and combination chemotherapy together with or without trastuzumab is more effective in treating esophageal cancer. Clinical data presented in the following publication(s):PMID 35038433Disease type(s): Gastrointestinal Neoplasm - Gastroesophageal CancerClinical Dataset(s) included:NCT01196390-D1 (PMID 35038433): There are three datasets for RTOG-1010's primary publication 35038433 (-D1 through -D3). This dataset, NCT01196390-D1, contains the baseline characteristics, treatment, reasons for treatment discontinuation, surgery information, survival, and toxicity data. NCT01196390-D2 (PMID 35038433): There are three datasets for RTOG-1010's primary publication 35038433 (-D1 through -D3). This dataset, NCT01196390-D2, contains the treatment-related adverse event data. NCT01196390-D3 (PMID 35038433): There are three datasets for RTOG-1010's primary publication 35038433 (-D1 through -D3). This dataset, NCT01196390-D3, contains the treatment-related serious adverse event data. You are encouraged to view the PDF data dictionaries found in the “Documents” tab of the dbGaP study page, which may contain additional information regarding the data or the associated publication(s).

Study phs004237

Translational Genomics in Cervical Cancer

This study characterizes the mutational trajectories of locally-advanced cervical cancer (LACC) cases during the course of standard of care chemoradiation therapy (CRT) treatment at Washington University School of Medicine. Tissue biopsied from primary LACC tumors prior to the start of therapy and at mid-treatment and normal blood were collected for sequencing. Whole exome sequencing (WES) was performed on the Illumina NovaSeq 6000 and whole genome sequencing (WGS) was performed on the Illumina NovaSeq X. The most frequently mutated genes and tumor mutational burden were consistent with previously published cervical cancer studies. Raw sequencing reads for all samples are made available here.

Study phs004441

Blockade of TGF Beta Drive Hyper Progression on Small Cell Lung Cancer

To uncover mechanisms underlying divergent outcomes in patients with small cell lung cancer (SCLC), a highly aggressive neuroendocrine malignancy, we performed bulk transcriptomics of pre-treatment tumor biopsies from patients enrolled in a clinical trial of bintrafusp alfa, a bifunctional fusion protein targeting PD-L1 and TGF-β. We identified marked elevation of IFN-γ signaling and MHC class II expression. In contrast, Hyperprogressive disease (HPD) was associated with systemic immune suppression, impaired cytotoxicity, and, unexpectedly, tumor-intrinsic activation of TGF-β signaling and stemness. Functional studies confirmed that intact TGFβR2-mediated signaling is required for the hyperproliferative response to TGF-β blockade, revealing a context-dependent tumor-suppressive role for TGF-β.Although TGF-β is widely regarded as an immunosuppressive driver in advanced cancers, our findings reveal a tumor-intrinsic, growth-constraining role for TGF-β signaling in SCLC. Disrupting this restraint can accelerate tumor progression, providing a mechanistic basis for HPD and highlighting the need for biomarker-driven strategies that account for tumor-intrinsic signaling when applying stromal-targeted immunotherapies.

Study phs004200

Genome Sequencing of Individuals with PTEN Hamartoma Tumor Syndrome

This study investigated genomic modifiers of cancer and neurodevelopmental outcomes among individuals with PTEN hamartoma tumor syndrome (PHTS), a rare hereditary disorder caused by germline PTEN variants and associated with broad clinical variability, including cancer predisposition, autism spectrum disorder, developmental delay, and intellectual disability. The primary aim was to determine whether additional inherited genomic variation beyond PTEN contributes to divergent clinical manifestations, particularly the development of cancer versus neurodevelopmental disorders.The main analytic cohort consisted of 543 probands with germline PTEN variants, including participants with cancer, neurodevelopmental disorders, both cancer and neurodevelopmental disorders, or neither phenotype at the time of consent.Molecular data were generated from germline DNA extracted from peripheral blood leukocytes using PCR-free whole-genome sequencing at approximately 30× coverage. Sequence reads were aligned to the hg38 human reference genome, followed by standard variant calling, quality control, annotation, and downstream genomic analyses. The study evaluated pathogenic or likely pathogenic variants in established cancer predisposition genes and neurodevelopmental disorder genes, and also performed genome-wide common-variant and rare-variant association analyses to identify candidate modifier loci.Principal findings showed that a subset of individuals with PHTS carried additional germline variants in known cancer- or neurodevelopment-related genes. Specifically, additional cancer-associated variants were identified in 37 of 543 probands, most commonly involving MITF, DICER1, and BRCA2, while neurodevelopment-associated variants were identified in 43 of 543 probands, including variants in DHCR7, POLG, ARSA, and other genes. Genome-wide analyses further identified candidate modifier loci with potential biological relevance to PTEN signaling and phenotype divergence, including ZNF713, TPTE2P1, and PDPK1. These findings support the hypothesis that PHTS clinical outcomes are influenced not only by germline PTEN variation, but also by additional inherited genomic modifiers.Data to be made available through dbGaP will include de-identified individual-level germline whole-genome sequencing data and associated phenotype information relevant to PHTS, cancer status, neurodevelopmental status, demographic variables, and PTEN variant classification, consistent with participant consent and institutional certification. The individual-level data are intended for controlled access.

Study phs004787

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