Downloads provided by UsageCountsSex Differences in Oncogenic Mutational Processes
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Constance H. Li; Stephenie D. Prokopec; Ren X. Sun; Fouad Yousif; Nathaniel Schmitz; Fatima Al-Shahrour; Gurnit Atwal; +193 Authors
Constance H. Li; 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; Ren X. Sun; Kevin Thai; Derek W. 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; Fatima Al-Shahrour; 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; Gurnit Atwal; Sietse Aukema; J. Todd Auman; Miriam R. Aure; Philip Awadalla; Marta Aymerich; Gary D. Bader; Adrian Baez-Ortega; Matthew H. Bailey; Peter J. 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; Andrew V. Biankin; 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; Arndt Borkhardt; Keith A. Boroevich; Ivan Borozan; Christoph Borst; Marcus Bosenberg; Mattia Bosio; Jacqueline Boultwood; Guillaume Bourque; Paul C. Boutros; G. Steven Bova; David T. Bowen; Reanne Bowlby; David D. L. Bowtell; Sandrine Boyault; Rich Boyce; Jeffrey Boyd; Alvis Brazma; Paul Brennan; Daniel S. Brewer; Arie B. Brinkman; Robert G. Bristow; Russell R. Broaddus; Jane E. Brock; Malcolm Brock; Annegien Broeks; Angela N. Brooks; Denise Brooks; Benedikt Brors; Søren Brunak; Timothy J. C. Bruxner; Alicia L. Bruzos; Alex Buchanan; Ivo Buchhalter; Christiane Buchholz; Susan Bullman; Hazel Burke; Birgit Burkhardt; Kathleen H. Burns; John Busanovich; Carlos D. Bustamante; Adam P. Butler; Atul J. Butte; Niall J. Byrne;
10.1101/528968 , 10.1038/s41467-020-17359-2 , 10.7892/boris.146651 , 10.17863/cam.57292 , 10.17863/cam.56829 , 10.17863/cam.74798
10230/53397 , 10261/236921 , 10651/61361 , 2445/175271 , https://repository.ubn.ru.nl/handle/2066/226014 , 10852/85452 , 2066/226014 , 10281/284732 , 11562/1032323 , 11577/3348317 , 20.500.11815/2171 , 1854/LU-8748408 , 10023/20993 , 11250/2764296 , 11571/1369454 , 11343/244392 , 1959.4/unsworks_73185 , 1721.1/129457 , 1959.7/uws:57776 , 2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/338729
10.1101/528968 , 10.1038/s41467-020-17359-2 , 10.7892/boris.146651 , 10.17863/cam.57292 , 10.17863/cam.56829 , 10.17863/cam.74798
10230/53397 , 10261/236921 , 10651/61361 , 2445/175271 , https://repository.ubn.ru.nl/handle/2066/226014 , 10852/85452 , 2066/226014 , 10281/284732 , 11562/1032323 , 11577/3348317 , 20.500.11815/2171 , 1854/LU-8748408 , 10023/20993 , 11250/2764296 , 11571/1369454 , 11343/244392 , 1959.4/unsworks_73185 , 1721.1/129457 , 1959.7/uws:57776 , 2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/338729
Sex Differences in Oncogenic Mutational Processes
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 describe the first pan-cancer analysis of sex differences in whole genomes of 1,983 tumours of 28 subtypes from the ICGC Pan-Cancer Analysis of Whole Genomes project. 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 cancer research. Sex disparities in cancer epidemiology include an increased overall cancer risk in males corresponding with higher incidence in most tumor types, even after adjusting for known risk factors 1,2 . Cancer mortality is also higher in males, due in part to better survival for female patients in many cancer types, including those of the colon and head & neck 3 . Interestingly, female colorectal cancer patients respond better to surgery 4 and adjuvant chemotherapy, though this is partially due to biases in tumour location and microsatellite instability 5 . Similarly, premenopausal female nasopharyngeal cancer patients have improved survival regardless of tumour stage, radiation or chemotherapy regimen 6 . There is a growing body of evidence for sex differences in cancer genomics 7-13 , but their molecular origins and clinical implications remain largely elusive. Previous studies have mostly focused on protein coding regions, leaving the vast majority of the genome unexplored. We hypothesized that there are uncharacterized sex differences in the non-coding regions of the genome. Using whole genome sequencing data from the Pan-cancer Analysis of Whole Genomes (PCAWG) project 14 , we performed a survey of sex-biased mutations in 1,983 samples (1,213 male, 770 female) from 28 tumour subtypes, excluding those of the sex organs ( Supplementary Table 1 ). We also excluded the X and Y chromosomes to focus on autosomal sex differences in cancers affecting both men and women, but there are known to be significant X-chromosome mutational differences between tumours arising in men and women 15 . Our analysis revealed sex differences in both genome-wide phenomena and in specific genes. These sex-biases occur not only at the pan-cancer level across all 1,983 samples, but also in individual tumour subtypes.
Switzerland, United States, Australia, United Kingdom, Spain, Belgium, United Kingdom, Spain, United Kingdom, Belgium, United States, Germany, Spain, Finland, Australia, Italy, Spain, Denmark, Norway, United Kingdom, Belgium, Netherlands, China (People's Republic of), Italy, Australia, Singapore, China (People's Republic of), Belgium, Singapore, Italy, Iceland, Italy, Croatia, Norway, United Kingdom, United Kingdom, Germany, Australia, United Kingdom
- Polish Academy of Sciences Poland
- University of copenhaguen Denmark
- University of Quensland Australia
- Western Sydney University Australia
- University of Oviedo Spain
sex differences, Male, Geschlechterdifferenz, oncogenes, 150, Kynferði, 32 Biomedical and Clinical Sciences, 3122, DISPARITIES, 318, Cancer genomics, Càncer, Cancer genetics, Genome informatics, Cancer genomics, Oncogenes, Cancer genetics, Cancer, anzsrc-for: 42 Health Sciences, Neoplasms -- genetics, Sciences bio-médicales et agricoles, 1600 Chemistry, Neoplasms/genetics, Radiation Oncology - Radboud University Medical Center, Science & Technology - Other Topics, anzsrc-for: 3102 Bioinformatics and Computational Biology, Human, Logistic Model, Science, Bioinformatics and Computational Biology, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, 610, 612, 320226 - Surgery, General Biochemistry, Genetics and Molecular Biology, Article, Genomic Instability, RC0254, Càncer -- Epidemiologia, Open Reading Frames, anzsrc-for: 32 Biomedical and Clinical Sciences, Cancer Genomics, SDG 3 - Good Health and Well-being, Chromosomal Instability, Health Sciences, Sex differences, Genetics, Humans, beta Catenin -- genetics, SIGNATURES, anzsrc-for: 3211 Oncology and Carcinogenesis, Krebs, Science & Technology, /45, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Oncogenes, 3211 Oncology and Carcinogenesis, Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life Sciences, Cancérologie, /692/4028/67/69, Genòmica, Laboratory Medicine - Radboud University Medical Center, Logistic Models, General Biochemistry, Mutation, PCAWG Tumour Subtypes and Clinical Translation, /119, 610 Medizin und Gesundheit, 31 Biological Sciences, Medizin, 200199 - Clinical health not elsewhere classified, General Physics and Astronomy, Genome informatics, 3102 Bioinformatics and Computational Biology, Neoplasms, /38/23, Medicine and Health Sciences, 2.1 Biological and endogenous factors, 3100 Physics and Astronomy, Exome, anzsrc-for: 31 Biological Sciences, beta Catenin, ddc:610, Sex Characteristics, Genome, 318 Medical biotechnology, Q, article, 3 Good Health and Well Being, 3rd-DAS, Biological Sciences, CANCER, Multidisciplinary Sciences, SURVIVAL, /631/114/2785, Female, Càncer -- Tractament, Oncogenes -- genetics, 1300 Biochemistry, beta Catenin/genetics, Oncology and Carcinogenesis, 3122 Cancers, Genetics and Molecular Biology, 610 Medicine & health, QH426 Genetics, Open Reading Frame, Cancer epidemiology, /631/67/68, Krabbameinsrannsóknir, cancer, QH426, Oncogene, Krabbamein, Oncogenes/genetics, Biomedical and Clinical Sciences, Genome, Human, Sex organs, Human Genome, 42 Health Sciences, PCAWG Consortium, General Chemistry, GENE, 3111, Good Health and Well Being, Cancer genetics ; Cancer genomics ; Genome informatics ; Oncogenes, Estudis de gènere, oncogenic mutational processes, /692/4028/67/395, Diferències entre sexes, Neoplasm, Women's Health, Gender studies, 3111 Biomedicine
sex differences, Male, Geschlechterdifferenz, oncogenes, 150, Kynferði, 32 Biomedical and Clinical Sciences, 3122, DISPARITIES, 318, Cancer genomics, Càncer, Cancer genetics, Genome informatics, Cancer genomics, Oncogenes, Cancer genetics, Cancer, anzsrc-for: 42 Health Sciences, Neoplasms -- genetics, Sciences bio-médicales et agricoles, 1600 Chemistry, Neoplasms/genetics, Radiation Oncology - Radboud University Medical Center, Science & Technology - Other Topics, anzsrc-for: 3102 Bioinformatics and Computational Biology, Human, Logistic Model, Science, Bioinformatics and Computational Biology, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, 610, 612, 320226 - Surgery, General Biochemistry, Genetics and Molecular Biology, Article, Genomic Instability, RC0254, Càncer -- Epidemiologia, Open Reading Frames, anzsrc-for: 32 Biomedical and Clinical Sciences, Cancer Genomics, SDG 3 - Good Health and Well-being, Chromosomal Instability, Health Sciences, Sex differences, Genetics, Humans, beta Catenin -- genetics, SIGNATURES, anzsrc-for: 3211 Oncology and Carcinogenesis, Krebs, Science & Technology, /45, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Oncogenes, 3211 Oncology and Carcinogenesis, Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life Sciences, Cancérologie, /692/4028/67/69, Genòmica, Laboratory Medicine - Radboud University Medical Center, Logistic Models, General Biochemistry, Mutation, PCAWG Tumour Subtypes and Clinical Translation, /119, 610 Medizin und Gesundheit, 31 Biological Sciences, Medizin, 200199 - Clinical health not elsewhere classified, General Physics and Astronomy, Genome informatics, 3102 Bioinformatics and Computational Biology, Neoplasms, /38/23, Medicine and Health Sciences, 2.1 Biological and endogenous factors, 3100 Physics and Astronomy, Exome, anzsrc-for: 31 Biological Sciences, beta Catenin, ddc:610, Sex Characteristics, Genome, 318 Medical biotechnology, Q, article, 3 Good Health and Well Being, 3rd-DAS, Biological Sciences, CANCER, Multidisciplinary Sciences, SURVIVAL, /631/114/2785, Female, Càncer -- Tractament, Oncogenes -- genetics, 1300 Biochemistry, beta Catenin/genetics, Oncology and Carcinogenesis, 3122 Cancers, Genetics and Molecular Biology, 610 Medicine & health, QH426 Genetics, Open Reading Frame, Cancer epidemiology, /631/67/68, Krabbameinsrannsóknir, cancer, QH426, Oncogene, Krabbamein, Oncogenes/genetics, Biomedical and Clinical Sciences, Genome, Human, Sex organs, Human Genome, 42 Health Sciences, PCAWG Consortium, General Chemistry, GENE, 3111, Good Health and Well Being, Cancer genetics ; Cancer genomics ; Genome informatics ; Oncogenes, Estudis de gènere, oncogenic mutational processes, /692/4028/67/395, Diferències entre sexes, Neoplasm, Women's Health, Gender studies, 3111 Biomedicine
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).107 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1% views 462 downloads 262 - 462views262downloads
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These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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