Sex differences in oncogenic mutational processes

PCAWG Tumour Subtypes and Clinical Translation; PCAWG Consortium; 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; Tapio Visakorpi; Steve Bova

doi:10.1038/s41467-020-17359-2

Sex differences in oncogenic mutational processes

PCAWG Tumour Subtypes and Clinical Translation, PCAWG Consortium, 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 GetzSean 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, Tapio Visakorpi, Steve Bova

TAYS Cancer Centre

Research output: Contribution to journal › Article › Scientific › peer-review

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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.

Original language	English
Article number	4330
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17359-2
Publication status	Published - 2020
Publication type	A1 Journal article-refereed

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Publication forum level 3

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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PCAWG Tumour Subtypes and Clinical Translation, PCAWG Consortium, Li, C. H., Prokopec, S. D., Sun, R. X., Yousif, F., Schmitz, N., Al-Shahrour, F., Atwal, G., Bailey, P. J., Biankin, A. V., Boutros, P. C., Campbell, P. J., Chang, D. K., Cooke, S. L., Deshpande, V., Faltas, B. M., Faquin, W. C., Garraway, L., ... Bova, S. (2020). Sex differences in oncogenic mutational processes. Nature Communications, 11(1), Article 4330. https://doi.org/10.1038/s41467-020-17359-2

@article{9d91d18555c2410b9d13dac4ff971ca8,

title = "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 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.",

author = "{PCAWG Tumour Subtypes and Clinical Translation} and {PCAWG Consortium} and Li, {Constance H.} and Prokopec, {Stephenie D.} and Sun, {Ren X.} and Fouad Yousif and Nathaniel Schmitz and Fatima Al-Shahrour and Gurnit Atwal and Bailey, {Peter J.} and Biankin, {Andrew V.} and Boutros, {Paul C.} and Campbell, {Peter J.} and Chang, {David K.} and Cooke, {Susanna L.} and Vikram Deshpande and Faltas, {Bishoy M.} and Faquin, {William C.} and Levi Garraway and Gad Getz and Grimmond, {Sean M.} and Syed Haider and Hoadley, {Katherine A.} and Wei Jiao and Kaiser, {Vera B.} and Rosa Karli{\'c} and Mamoru Kato and Kirsten K{\"u}bler and Lazar, {Alexander J.} and Li, {Constance H.} and Louis, {David N.} and Adam Margolin and Sancha Martin and Nahal-Bose, {Hardeep K.} and Nielsen, {G. Petur} and Serena Nik-Zainal and Larsson Omberg and Christine P{\textquoteright}ng and Perry, {Marc D.} and Paz Polak and Esther Rheinbay and Rubin, {Mark A.} and Semple, {Colin A.} and Sgroi, {Dennis C.} and Tatsuhiro Shibata and Reiner Siebert and Jaclyn Smith and Stein, {Lincoln D.} and Stobbe, {Miranda D.} and Sun, {Ren X.} and Kevin Thai and Tapio Visakorpi and Steve Bova",

note = "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. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

doi = "10.1038/s41467-020-17359-2",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

PCAWG Tumour Subtypes and Clinical Translation, PCAWG Consortium, Li, CH, Prokopec, SD, Sun, RX, Yousif, F, Schmitz, N, Al-Shahrour, F, Atwal, G, Bailey, PJ, Biankin, AV, Boutros, PC, Campbell, PJ, Chang, DK, Cooke, SL, Deshpande, V, Faltas, BM, Faquin, WC, Garraway, L, Getz, G, Grimmond, SM, Haider, S, Hoadley, KA, Jiao, W, Kaiser, VB, Karlić, R, Kato, M, Kübler, K, Lazar, AJ, Li, CH, Louis, DN, Margolin, A, Martin, S, Nahal-Bose, HK, Nielsen, GP, Nik-Zainal, S, Omberg, L, P’ng, C, Perry, MD, Polak, P, Rheinbay, E, Rubin, MA, Semple, CA, Sgroi, DC, Shibata, T, Siebert, R, Smith, J, Stein, LD, Stobbe, MD, Sun, RX, Thai, K, Visakorpi, T & Bova, S 2020, 'Sex differences in oncogenic mutational processes', Nature Communications, vol. 11, no. 1, 4330. https://doi.org/10.1038/s41467-020-17359-2

TY - JOUR

T1 - Sex differences in oncogenic mutational processes

AU - PCAWG Tumour Subtypes and Clinical Translation

AU - PCAWG Consortium

AU - Li, Constance H.

AU - Prokopec, Stephenie D.

AU - Sun, Ren X.

AU - Yousif, Fouad

AU - Schmitz, Nathaniel

AU - Al-Shahrour, Fatima

AU - Atwal, Gurnit

AU - Bailey, Peter J.

AU - Biankin, Andrew V.

AU - Boutros, Paul C.

AU - Campbell, Peter J.

AU - Chang, David K.

AU - Cooke, Susanna L.

AU - Deshpande, Vikram

AU - Faltas, Bishoy M.

AU - Faquin, William C.

AU - Garraway, Levi

AU - Getz, Gad

AU - Grimmond, Sean M.

AU - Haider, Syed

AU - Hoadley, Katherine A.

AU - Jiao, Wei

AU - Kaiser, Vera B.

AU - Karlić, Rosa

AU - Kato, Mamoru

AU - Kübler, Kirsten

AU - Lazar, Alexander J.

AU - Li, Constance H.

AU - Louis, David N.

AU - Margolin, Adam

AU - Martin, Sancha

AU - Nahal-Bose, Hardeep K.

AU - Nielsen, G. Petur

AU - Nik-Zainal, Serena

AU - Omberg, Larsson

AU - P’ng, Christine

AU - Perry, Marc D.

AU - Polak, Paz

AU - Rheinbay, Esther

AU - Rubin, Mark A.

AU - Semple, Colin A.

AU - Sgroi, Dennis C.

AU - Shibata, Tatsuhiro

AU - Siebert, Reiner

AU - Smith, Jaclyn

AU - Stein, Lincoln D.

AU - Stobbe, Miranda D.

AU - Sun, Ren X.

AU - Thai, Kevin

AU - Visakorpi, Tapio

AU - Bova, Steve

N1 - 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. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-17359-2

DO - 10.1038/s41467-020-17359-2

M3 - Article

C2 - 32859912

AN - SCOPUS:85079052881

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4330

ER -

Sex differences in oncogenic mutational processes

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