Genetic Determinants of Somatic Selection of Mutational Processes in 3,566 Human Cancers

Overview

Journal Cancer Res

Specialty Oncology

Date 2021 Jul 3

PMID 34215622

Citations 7

Authors

Jintao Guo

Ying Zhou

Chaoqun Xu

Qinwei Chen

Zsofia Sztupinszki

Judit Borcsok

Canqiang Xu

Feng Ye

Weiwei Tang

Jiapeng Kang

Lu Yang

Jiaxin Zhong

Taoling Zhong

Tianhui Hu

Rongshan Yu

Zoltan Szallasi

Xianming Deng

Qiyuan Li

Affiliations

Soon will be listed here.

Abstract

The somatic landscape of the cancer genome results from different mutational processes represented by distinct "mutational signatures." Although several mutagenic mechanisms are known to cause specific mutational signatures in cell lines, the variation of somatic mutational activities in patients, which is mostly attributed to somatic selection, is still poorly explained. Here, we introduce a quantitative trait, mutational propensity (MP), and describe an integrated method to infer genetic determinants of variations in the mutational processes in 3,566 cancers with specific underlying mechanisms. As a result, we report 2,314 candidate determinants with both significant germline and somatic effects on somatic selection of mutational processes, of which, 485 act via cancer gene expression and 1,427 act through the tumor-immune microenvironment. These data demonstrate that the genetic determinants of MPs provide complementary information to known cancer driver genes, clonal evolution, and clinical biomarkers. SIGNIFICANCE: The genetic determinants of the somatic mutational processes in cancer elucidate the biology underlying somatic selection and evolution of cancers and demonstrate complementary predictive power across cancer types.

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