Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.

ABSTRACT:

Background

Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic.

Results

Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirica

SUBMITTER: Zapata L 

PROVIDER: S-EPMC5984361 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature