Search Results - EGA European Genome-Phenome Archive

Whole genome sequencing

The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. We performed whole genome sequencing on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking, or received neoadjuvant chemotherapy (NACT) with excellent or poor response.

Dataset EGAD00001005240

panel data of ALK-positiv non-small cell lung cancer patients

270 samples with ALK-positiv non-small cell lung cancer, targeted sequencing (198 kb panel size)

Dataset EGAD00001006297

Predictor_ChemoNEAR_TNBC (2019-08-14)

In this study a collection of core biopsies from breast cancer patients receiving neoadjuvant chemotherapy as part of the ChemoNEAR trial will be investigated. The study is intended to detect early acquired resistance in women with diagnosed breast carcinoma. Samples will undergo whole genome sequencing and analysis, including use of HR Predict. . This dataset contains all the data available for this study on 2019-08-14.

Dataset EGAD00001005255

MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma

The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute. Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

Study EGAS00001002608

TCR β-chain repertoire characterization of regulatory and conventional T cells in peripheral blood from breast cancer patients and healthy individuals.

Identification of tumor-specific effects on peripheral TCRβ repertoire formation in humans, investigation of the clonal origin of regulatory T cells in breast cancer patients and impact analysis of the tumor-specific conversion of conventional T cells into induced regulatory T cells on the peripheral Treg repertoire in humans.

Study EGAS00001002699

Preferential infiltration of distinct Vγ9δ2 T cells into Glioblastoma multiforme

Glioblastoma multiforme (GBM), the most fatal CNS cancer, is highly infiltrative as a result of phenotypic alteration of cancer cells mainly driven by a mutual interaction among cancer cells, tumor-associated macrophages (TAMs) and other stromal cells. This work aims at characterizing GBM-infiltrating γδ T cells that may regulate the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumor-infiltrating and blood circulating γδ T cells from 4 patients were analyzed by NGS-based TCR sequencing. RNA gene expression profiling and immunostaining of cancer tissues were performed as well.

Study EGAS00001002790

Sensitive and Frequent Identification of High Avidity Neo-epitope Specific CD8 + T-cells in Immunotherapy-naïve Ovarian Cancer

Immunotherapy directed against private tumor neo-antigens derived from non-synonymous somatic mutations is a promising strategy of personalized cancer immunotherapy. However, feasibility in low mutational load tumor types remains unknown. Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neo-epitope specific CD8 + T cells allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naïve patients with advanced epithelial ovarian cancer studied. Neo-epitope recognition was discordant between circulating T cells and TILs, and was more likely to be found among TILs, which displayed higher functionalavidity and unique TCRs with higher predicted affinity than their blood counterparts. Our results imply that identification of neo-epitope specific CD8 + T cells is achievable even in tumors with relatively low number of somatic mutations, and neo-epitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.

Study EGAS00001002803

Pan Prostate Cancer Group data

The Pan Prostate Cancer Group intends to provide breakthrough advances from the analysis of a very large series of Whole Genome DNA data, contributed by many of the leading scientists and clinicians working in prostate cancer genomics generating Whole Genome DNA Sequence (WGS) data from prostate cancer patients. The accumulated data, collected and compared in a common format including common storage, re-analysis through a single pipeline, and investigation to achieve a variety of scientific goals, are presented in this series. This project will provide a global framework for the future analysis of even larger series of genomes as costs of DNA sequencing, storage, and sequence analysis decrease. In addition to these WGS data from different clinical categories, ethnicities, levels of aggressiveness, and disease managed by different treatments with information linked to long-term clinical follow up, we intend to add additional layers of data, including transcriptome and methylation data. The current data series focuses primarily on the analysis of WGS data. For further information, please refer to https://panprostate.org/, and The Pan Prostate Cancer Group Data Sharing Policy, EGAP50000000784.

Study EGAS00001002876

“Castration-persistence” is a distinct state of tolerance to androgen receptor targeting therapies in prostate cancer

Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive progressive ‘castration resistant’ disease are reasonably well characterized, how tumours survive acute pathway inhibition is unclear. We performed a neo-adjuvant study of a novel combination of AR targeting therapies, and noted that the objective response to treatment was highly variable. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples were using both whole genome and RNA-sequencing. We find that ‘castration-persistence’ is a distinct state from ‘castration-resistance’, and is mediated by global transcriptional reprogramming leading to transitional EMT state, which is shared with benign luminal epithelial cells. This appears to be AP-1 and KLF driven, and represents and integration of multiple signalling pathways, particularly IGF2, offering a number of tractable strategies to improve clinical response to AR targeting therapies.

Study EGAS00001003172

TCR β-chain repertoire characterization of regulatory and conventional T cells in breast tumors from breast cancer patients.