Frequency of theTMPRSS2:ERGgene fusion is increased in moderate to poorly differentiated prostate cancers

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Abstract
Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes,ERGorETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine proteaseTMPRSS2(21q22.2) to the 3′ end of eitherERG(21q22.3) orETV1(7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes,ETV1orERG.Aim: To determine the frequency of rearrangements involvingTMPRSS2,ERG, orETV1genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs).Methods: Two independent assays, aTMPRSS2break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis.Results: A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements.TMPRSS2:ERGfusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017).TMPRSS2:ETV1gene fusions were not detected in any of the cases tested.TMPRSS2:ERGfusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed.Conclusion: This study indicates thatTMPRSS2:ERGgene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.

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