Functional and genetic determinants of mutation rate variability in regulatory elements of cancer genomes.

ABSTRACT:

Background

Cancer genomes are shaped by mutational processes with complex spatial variation at multiple scales. Entire classes of regulatory elements are affected by local variations in mutation frequency. However, the underlying mechanisms with functional and genetic determinants remain poorly understood.

Results

We characterise the mutational landscape of 1.3 million gene-regulatory and chromatin architectural elements in 2419 whole cancer genomes with transcriptional and pathway activity, functional conservation and recurrent driver events. We develop RM2, a statistical model that quantifies mutational enrichment or depletion in classes of genomic elements through genetic, trinucleotide and megabase-scale effects. We report a map of localised mutational processes affectin

SUBMITTER: Lee CA 

PROVIDER: S-EPMC8091793 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature