Sex differences in oncogenic mutational processes

被引：64

作者：

Li, Constance H. ^{[1
,2
,3
]}

Prokopec, Stephenie D. ^{[1
]}

Sun, Ren X. ^{[1
,4
]}

Yousif, Fouad ^{[1
]}

Schmitz, Nathaniel ^{[1
]}

Boutros, Paul C. ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

机构：

[1] Ontario Inst Canc Res, Computat Biol Program, Toronto, ON, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[3] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90032 USA

[4] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[5] Vector Inst Artificial Intelligence, Toronto, ON, Canada

[6] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA 90032 USA

[7] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[8] Univ Calif Los Angeles, Inst Precis Hlth, Los Angeles, CA 90032 USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会; 加拿大创新基金会;

关键词：

CANCER; DISPARITIES; SURVIVAL; SIGNATURES; GENE;

D O I：

10.1038/s41467-020-17359-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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