Gene Fusions in Prostate Cancer

Abstract

Recurrent chromosomal rearrangements resulting in the fusion of androgen regulated genes with ETS transcription factor family members ERG or ETV1 are the most common molecular abnormality in prostate cancer. In the ensuing decade since this discovery, enormous progress has been made in understanding the diversity, biogenesis, and function of ETS gene fusions, both in vitro and in vivo. ETS gene fusions and associated co-occurring or mutually exclusive genetic events provide a rational basis for the comprehensive molecular subtyping of prostate cancer with potential utility for precision medicine approaches. As the most specific known biomarker in prostate cancer, ETS gene fusions may have utility in tissue based diagnosis, risk stratification of precursor lesions, early detection, and distinguishing between clinically aggressive and indolent cases of prostate cancer. While the vast majority of recurrent gene rearrangements in prostate cancer involve the ETS gene family, additional low frequency fusion events involving known oncogenes BRAF, KRAS, RAF1, and FGFR2 have also been described. These rare events suggest that small subsets of prostate cancer patients harbour fusion events with immediate clinical significance and are candidates for targeted therapy.