Sex differences in oncogenic mutational processes
Constance H. Li, Stephenie D. Prokopec, Ren Sun, Fouad Yousif, Nathaniel Schmitz, Fátima Al‐Shahrour, Gurnit Atwal, Peter J. Bailey, Andrew V. Biankin, Paul C. Boutros, Peter J. Campbell, David K. Chang, Susanna L. Cooke, Vikram Deshpande, Bishoy M. Faltas, William C. Faquin, Levi A. Garraway, Gad Getz, Sean M. Grimmond, Syed Haider, Katherine A. Hoadley, Wei Jiao, Vera B. Kaiser, Rosa Karlić, Mamoru Kato, Kirsten Kübler, Alexander J. Lazar, Constance H. Li, David N. Louis, Adam Margolin, Sancha Martin, Hardeep K. Nahal-Bose, G. Petur Nielsen, Serena Nik‐Zainal, Larsson Omberg, Christine P’ng, Marc D. Perry, Paz Polak, Esther Rheinbay, Mark A. Rubin, Colin A. Semple, Dennis C. Sgroi, Tatsuhiro Shibata, Reiner Siebert, Jaclyn Smith, Lincoln Stein, Miranda D. Stobbe, Ren Sun, Kevin Thai, Derek Wright, Chin‐Lee Wu, Ke Yuan, Junjun Zhang, Paul C. Boutros, Lauri A. Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J. Adams, Nishant Agrawal, Keun Soo Ahn, Sung-Min Ahn, Hiroshi Aikata, Rehan Akbani, Kadir C. Akdemir, Hikmat Al‐Ahmadie, Sultan T. Al‐Sedairy, Fátima Al‐Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B. Alexandrov, Adrian Ally, Kathryn Alsop, Eva G. Álvarez, Fernanda Amary, Samirkumar B. Amin, Brice Aminou, Ole Ammerpohl, Matthew J. Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparício, Elizabeth L. Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun‐ichi Ariizumi, Joshua Armenia, Laurent Arnould, L. Sylvia, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J. Todd Auman, Miriam R. R. Aure, Philip Awadalla, Marta Aymerich, Gary D. Bader
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.