作者
Stephenie D Prokopec, Ren X Sun, Fouad Yousif, Nathaniel Schmitz, Fatima 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 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 D Stein, Miranda D Stobbe, Kevin Thai, Derek W Wright, Chin-Lee Wu, Ke Yuan, Junjun Zhang, 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, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B Alexandrov, Adrian Ally, Kathryn Alsop, Eva G Alvarez, Fernanda Amary, Samirkumar B Amin, Brice Aminou, Ole Ammerpohl, Matthew J Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun-ichi Ariizumi, Joshua Armenia, Laurent Arnould, Sylvia Asa, Yassen Assenov, Sietse Aukema, J Todd Auman, Miriam R Aure, Philip Awadalla, Marta Aymerich, Gary D Bader, Adrian Baez-Ortega, Matthew H Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E Banks, Stefano Barbi, Andrew P Barbour, Jonathan Barenboim, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B Baylin, Wojciech Bazant, Duncan Beardsmore, Timothy A Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltran, Christopher Benz, Andrew Berchuck, Anke K Bergmann, Erik N Bergstrom, Benjamin P Berman, Daniel M Berney, Stephan H Bernhart, Rameen Beroukhim, Mario Berrios, Samantha Bersani, Johanna Bertl, Miguel Betancourt, Vinayak Bhandari, Shriram G Bhosle, Matthias Bieg, Darell Bigner, Hans Binder, Ewan Birney, Michael Birrer, Nidhan K Biswas, Bodil Bjerkehagen, Tom Bodenheimer, Lori Boice, Giada Bonizzato, Johann S De Bono, Arnoud Boot, Moiz S Bootwalla, Ake Borg
发表日期
2020/8/28
出版商
Nature Publishing Group UK
简介
Results
Sex-biases in driver genes, mutation load and tumour evolution. We began by investigating sex differences in driver gene mutation frequencies, focusing on 165 coding and nine noncoding mutation events 14 (Supplementary Data 2). We used proportion tests to identify candidate sex-biased events with a false discovery rate (FDR) threshold of 10%. These putative sexbiased events were modelled using logistic regression (LGR) to adjust for tumour subtype-specific variables (model descriptions and variable breakdown in Supplementary Data 1). Finally, we vetted these sex-biased events in two ways: we assessed the impact of covariate imbalances in the data using repeated down-sampling analysis; we also implemented extended regression models to adjust for additional variables like stage or grade, which were only available for a greatly reduced subset of the data (see “Methods” section). We confirmed that all sex-biases remained significant under this additional scrutiny. This statistical framework formed the basis for our analysis of all genomic features.
Tumour subtype-specific sex-biased driver mutations included CTNNB1 mutation frequency in liver hepatocellular cancer (Liver-HCC), with more male-derived samples harbouring CTNNB1 mutations:(male: 31%, female: 13%, 95% CI: 8.1–28%, prop-test q= 0.048, LGR q= 1.4× 10− 3, Fig. 1 a, Supplementary Fig. 1). This mirrors our previous finding of sex-biased CTNNB1 mutation frequency in liver cancer from TCGA exome sequencing data, with similar effect sizes (male: 33% vs. female: 12% 11). We also identified a large sex-disparity in a non-coding driver event in
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