Retention of interstitial genes between TMPRSS2 and ERG is associated with low-risk prostate cancer.

Although TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, the clinical impact of this fusion has been limited. Recently the retention of interstitial genes between TMPRSS2 and ERG was reported to influence tumor progression in an animal model. We therefore characterized the TMPRSS2-ERG fusion, including the status of the interstitial genes, in a large cohort of men treated surgically for prostate cancer and associated these fusion alterations with biochemical progression. Through whole genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate- and high-risk prostate cancer from radical prostatectomy specimens. TMPRSS2-ERG gene fusions were observed in 44% of cases, with over 90% of fusions occurring at exons 3 or 4 of ERG. ERG fusions that retained interstitial sequences were more frequently observed in very low-riskcancer. Identification of these patients at the time of biopsy could potentially improve patient management particularly in regards to active surveillance.