Cancer genomes tolerate deleterious coding mutations through somatic copy number amplifications of wild-type regions.

ABSTRACT: Cancers evolve under the accumulation of thousands of somatic mutations and chromosomal aberrations. While most coding mutations are deleterious, almost all protein-coding genes lack detectable signals of negative selection. This raises the question of how tumors tolerate such large amounts of deleterious mutations. Using 8,690 tumor samples from The Cancer Genome Atlas, we demonstrate that copy number amplifications frequently cover haploinsufficient genes in mutation-prone regions. This could increase tolerance towards the deleterious impact of mutations by creating safe copies of wild-type regions and, hence, protecting the genes therein. Our findings demonstrate that these potential buffering events are highly influenced by gene functions, essentiality, and mutation impact and that the

SUBMITTER: Alfieri F 

PROVIDER: S-EPMC10276008 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature