Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Nat Commun. 2020 Aug 28;11(1):4330. doi: 10.1038/s41467-020-17359-2.
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.
在癌症流行病学、治疗和生物学的多个方面，以及在除性器官以外的大多数癌症中，都观察到了性别差异。将这些临床差异与特定的分子特征联系起来的努力，主要集中在基因组编码区域内的体细胞突变上。在这里，我们报告了作为 ICGC/TCGA 全基因组泛癌分析（PCAWG）联盟的一部分，对 28 个亚型的 1983 个肿瘤的全基因组进行的性别差异的泛癌分析。我们既确认了外显子组研究的结果，也揭示了以前未描述的性别差异。这些差异包括编码和非编码癌症驱动因素、突变发生率，以及与潜在突变过程相关的突变特征方面的性别偏向。这些结果强调了分子性别差异的普遍性，并加强了在分子癌症研究中增加对性别的考虑的呼吁。
