Prevalence of TMPRSS2–ERGand SLC45A3–ERGgene fusions in a large prostatectomy cohort

The majority of prostate cancers harbor recurrent gene fusions between the hormone-regulated TMPRSS2and members of the ETS family of transcription factors, most commonly ERG. Prostate cancer with ERGrearrangements represent a distinct sub-class of tumor based on studies reporting associations with histomorphologic features, characteristic somatic copy number alterations, and gene expression signatures. This study describes the frequency of ERGrearrangement prostate cancer and three 5 prime (5′) gene fusion partners (ie, TMPRSS2, SLC45A3,and NDRG1) in a large prostatectomy cohort. ERGgene rearrangements and mechanism of rearrangement, as well as rearrangements of TMPRSS2, SLC45A3,and NDRG1,were assessed using fluorescence in situhybridization (FISH) on prostate cancer samples from 614 patients treated using radical prostatectomy. ERGrearrangement occurred in 53% of the 540 assessable cases. TMPRSS2and SLC45A3were the only 5′ partner in 78% and 6% of these ERGrearranged cases, respectively. Interestingly, 11% of the ERG rearranged cases showed concurrent TMPRSS2and SLC45A3rearrangements. TMPRSS2or SLC45A3rearrangements could not be identified for 5% of the ERGrearranged cases. From these remaining cases we identified one case with NDRG1rearrangement. We did not observe any associations with pathologic parameters or clinical outcome. This is the first study to describe the frequency of SLC45A3–ERGfusions in a large clinical cohort. Most studies have assumed that all ERGrearranged prostate cancers harbor TMPRSS2–ERGfusions. This is also the first study to report concurrent TMPRSS2and SLC45A3rearrangements in the same tumor focus, suggesting additional complexity that had not been previously appreciated. This study has important clinical implications for the development of diagnostic assays to detect ETS rearranged prostate cancer. Incorporation of these less common ERGrearranged prostate cancer fusion assays could further increase the sensitivity of the current PCR-based approaches.