LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint

Abstract

Significance In addition to canonical genes, our genomes encode repetitive copies of the LINE-1 retrotransposon. These elements duplicate themselves by cutting a single-strand break in genomic DNA and then reverse transcribing a new LINE-1 DNA copy into that breakpoint. In most contexts, LINE-1 elements are epigenetically repressed, but they are dramatically derepressed in many cancers, where they have the potential to impact genome integrity. We probed publicly available multiomic data from the CPTAC to identify the DNA damage response correlates of LINE-1 expression and validated the potential for LINE-1 overexpression to trigger RAD50 phosphorylation—a key step in an S phase double-strand break response pathway that we found to be highly correlated with LINE-1 expression in endometrial cancer.