Mutation hotspots at CTCF binding sites coupled to chromosomal instability in gastrointestinal cancers.

ABSTRACT: Tissue-specific driver mutations in non-coding genomic regions remain undefined for most cancer types. Here, we unbiasedly analyze 212 gastric cancer (GC) whole genomes to identify recurrently mutated non-coding regions in GC. Applying comprehensive statistical approaches to accurately model background mutational processes, we observe significant enrichment of non-coding indels (insertions/deletions) in three gastric lineage-specific genes. We further identify 34 mutation hotspots, of which 11 overlap CTCF binding sites (CBSs). These CBS hotspots remain significant even after controlling for a genome-wide elevated mutation rate at CBSs. In 3 out of 4 tested CBS hotspots, mutations are nominally associated with expression change of neighboring genes. CBS hotspot mutations are enriched in tu

SUBMITTER: Guo YA 

PROVIDER: S-EPMC5906695 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature