Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure.

ABSTRACT: Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mu

SUBMITTER: Akdemir KC 

PROVIDER: S-EPMC8350746 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature