Identifying DNase I hypersensitive sites as driver distal regulatory elements in breast cancer.

ABSTRACT: Efforts to identify driver mutations in cancer have largely focused on genes, whereas non-coding sequences remain relatively unexplored. Here we develop a statistical method based on characteristics known to influence local mutation rate and a series of enrichment filters in order to identify distal regulatory elements harboring putative driver mutations in breast cancer. We identify ten DNase I hypersensitive sites that are significantly mutated in breast cancers and associated with the aberrant expression of neighboring genes. A pan-cancer analysis shows that three of these elements are significantly mutated across multiple cancer types and have mutation densities similar to protein-coding driver genes. Functional characterization of the most highly mutated DNase I hypersensitive sites i

SUBMITTER: D Antonio M 

PROVIDER: S-EPMC5585396 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature