Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.

ABSTRACT: Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fi

SUBMITTER: Buckley MA 

PROVIDER: S-EPMC6359979 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature