Sex differences in oncogenic mutational processes
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., Wright DW., Wu CL., Yuan K., Zhang J., Boutros PC., Aaltonen LA., Abascal F., Abeshouse A., Aburatani H., Adams DJ., Agrawal N., Ahn KS., Ahn SM., Aikata H., Akbani R., Akdemir KC., Al-Ahmadie H., Al-Sedairy ST., Al-Shahrour F., Alawi M., Albert M., Aldape K., Alexandrov LB., Ally A., Alsop K., Alvarez EG., Amary F., Amin SB., Aminou B., Ammerpohl O., Anderson MJ., Ang Y., Antonello D., Anur P., Aparicio S., Appelbaum EL., Arai Y., Aretz A., Arihiro K., Ariizumi SI., Armenia J., Arnould L., Asa S., Assenov Y., Atwal G., Aukema S., Auman JT., Aure MR., Awadalla P., Aymerich M., Bader GD.
© 2020, The Author(s). 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.