Aberrant expression impacts the pan-cancer genomic landscape.

The binding of PRDM9 to chromatin is a key step in the induction of DNA double-strand breaks associated with meiotic recombination hotspots; it is normally expressed solely in germ cells. We interrogated 1879 cancer samples in 39 different cancer types and found that is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of in tumors are significantly higher than those found in healthy neighboring tissues and in healthy nongerm tissue databases. Recurrently mutated regions located within 5 Mb of the loci, as well as differentially expressed genes in meiotic pathways, correlate with expression. In samples with aberrant expression, structural variant breakpoints frequently neighbor the DNA motif recognized by PRDM9, and there is an enrichment of structural variants at sites of known meiotic PRDM9 activity. This study is the first to provide evidence of an association between aberrant expression of the meiosis-specific gene with genomic instability in cancer.