EGAS00001003542-sc-2020-12-08T14:37:12Z - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006732 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence – sequence data (Mutographs)
| EGAD00001006868 | EGA
Project description:Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence – filtered vcf files
| EGAD00001008339 | EGA
Project description:<p>International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not been identified by conventional epidemiology yet potentially make a substantial contribution to cancer burden1. This pertains to clear cell renal cell carcinoma (ccRCC), for which obesity, hypertension, and tobacco smoking are risk factors but do not explain its geographical variation in incidence2. Some carcinogens generate somatic mutations and a complementary strategy for detecting past exposures is to sequence the genomes of cancers from populations with different incidence rates and infer underlying causes from differences in patterns of somatic mutations. Here, we sequenced 962 ccRCC from 11 countries of varying incidence. Somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures likely caused by extracts of Aristolochia plants were present in most cases and rare elsewhere. In Japan, a mutational signature of unknown cause was found in >70% cases and <2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher kidney cancer incidence rates (p-value <6 × 10−18). Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension suggesting non-mutagenic mechanisms of action underlying these risk factors. The results indicate the existence of multiple, geographically variable, mutagenic exposures potentially affecting 10s of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (<strong>Mutographs</strong>) associated with this study are available in the <strong>European Genome-Phenome Archive</strong>: https://ega-archive.org/datasets/EGAD00001012223.</p>
2024-03-26 | MTBLS9394 | MetaboLights
Project description: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.
| EGAD00001006427 | EGA
Project description:Geographic variation of mutagenic exposures in kidney cancer genomes – sequence data (Mutographs)
| EGAD00001012102 | EGA
Project description:Geographic variation of mutagenic exposures in kidney cancer genomes – patient metadata files (Mutographs)
| EGAD00001012223 | EGA
Project description:Geographic variation of mutagenic exposures in kidney cancer genomes – filtered vcf files (Mutographs)
| EGAD00001012222 | EGA
Project description:Geographic variation of mutagenic exposures in kidney cancer genomes – copy number variants (Mutographs)
| EGAD00001013727 | EGA
Project description:Geographic variation of mutagenic exposures in kidney cancer genomes – structural variation vcf files ( Mutographs )
| EGAD00001013726 | EGA
Project description:Oral and esophageal squamous cell carcinomas (SCCs) are associated with high mortality, yet molecular mechanisms underlying these malignancies are largely unknown. We demonstrate that epigenetic silencing of otubain 2 (OTUB2), a previously recognized oncogene, drives SSCs initiation and drug resistance. Mechanistically, OTUB2 promotes deubiquitination and phosphorylation of signal transducer and activator of transcription 1 (STAT1), then activates transcriptional regulation of calmodulin-like protein 3 (CALML3). Activation of CALML3-mediated mitochondrial calcium signaling promotes oxidative phosphorylation (OXPHOS) and glycerophospholipid synthesis, among which phosphatidylserine (PS) is the most obviously affected. Orally administered soybean-derived PS dramatically inhibits low-OTUB2-expressed SCC initiation and increased sensitivity to chemotherapy in various mouse models. Our study indicates that the OTUB2/STAT1/CALML3/PS axis plays a critical tumor-suppressive role in SCCs, clarifies the low incidence of oral and esophageal SCCs in Western countries with a high-fat diet and demonstrates the potential of food supplementation with PS as a strategy for treatment and prevention of SCCs.
2022-09-19 | GSE172001 | GEO