Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers
- Melinda A Miller (memiller{at}bccancer.bc.ca)
- Alessandro De Luca (alessandro.deluca{at}vch.ca)
- Antonio Hurtado-Coll (antonio.hurtadocoll{at}vch.ca)
- Martin E Gleave (gleave{at}interchange.ubc.ca)
Abstract
Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5’ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3’ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG.
Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescent in situ hybridization (FISH) on CaP tissue microarrays (TMAs).
Methods: Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase - polymerase chain reaction (RT-PCR) and DNA sequence analysis.
Results: 106/196 (54.1%) cases were analyzed by FISH. None of the five benign prostatic hyperplasia cases analyzed exhibited these gene rearrangements. TMPRSS2:ERG fusion 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:ETV1 gene rearrangement was not detected in all of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNAsequencing in 7/7 randomly selected positive cases analysed.
Conclusion: This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.
