Sex differences in oncogenic mutational processes

Li, Constance H., Prokopec, Stephenie D., Sun, Ren X., Yousif, Fouad, Schmitz, Nathaniel, Al-Shahrour, Fatima, Boutros, Paul C., , PCAWG Tumour Subtypes and Clinical Translation and , PCAWG Consortium (2020) Sex differences in oncogenic mutational processes. Nature Communications, 11 (1). ISSN 2041-1723

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Abstract

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.

Item Type: Article
Additional Information: Funding Information: We thank all the members of the Boutros lab for insightful discussions. This study was conducted with the support of the Ontario Institute for Cancer Research to P.C.B. through funding provided by the Government of Ontario. This work was supported by the Discovery Frontiers: Advancing Big Data Science in Genomics Research program, which is jointly funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canadian Institutes of Health Research (CIHR), Genome Canada and the Canada Foundation for Innovation (CFI). P.C.B. was supported by a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award. This work was supported by an NSERC Discovery grant and by Canadian Institutes of Health Research, grant #SVB-145586, to P.C.B. This work was supported by the NIH/NCI under award number P30CA016042 and an operating grant from the National Cancer Institute Early Detection Research Network (1U01CA214194-01). We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.
Uncontrolled Keywords: chemistry(all),biochemistry, genetics and molecular biology(all),general,physics and astronomy(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 20 Jul 2022 09:30
Last Modified: 12 Aug 2022 05:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/86707
DOI: 10.1038/s41467-020-17359-2

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