RT Journal
A1 Houle, Armande Ang
A1 Gibling, Heather
A1 Lamaze, Fabien C.
A1 Edgington, Hilary A.
A1 Soave, David
A1 Fave, Marie-Julie
A1 Agbessi, Mawusse
A1 Bruat, Vanessa
A1 Stein, Lincoln D.
A1 Awadalla, Philip
T1 Aberrant PRDM9 expression impacts the pan-cancer genomic landscape
JF Genome Research 
JO Genome Research 
YR 2018 
FD November 01 
VO 28 
IS 11 
SP 1611 
OP 1620 
DO 10.1101/gr.231696.117 
UL http://genome.cshlp.org/content/28/11/1611.abstract 
AB 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 PRDM9 is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of PRDM9 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 PRDM9 loci, as well as differentially expressed genes in meiotic pathways, correlate with PRDM9 expression. In samples with aberrant PRDM9 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 PRDM9 with genomic instability in cancer.