Aberrant PRDM9 expression impacts the pan-cancer genomic landscape

• DOI: 10.1101/gr.231696.117
• Publication Date: 2018-10-19T15:46:49Z
• Authors: Armande Ang Houle; Heather Gibling; Fabien C. Lamaze; Hilary A. Edgington; David Soave; Marie-Julie Fave; Mawusse Agbessi; Vanessa Bruat; Lincoln D. Stein; Philip Awadalla
• Keywords: 0301 basic medicine; Chromosome Breakpoints; 03 medical and health sciences; Mutation Rate; Research; Neoplasms; Gene Expression Regulation, Developmental; Humans; Histone-Lysine N-Methyltransferase; Genomic Instability; 3. Good health

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