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ORIGINAL ARTICLES |
1 Genetic Pathology Evaluation Centre, Vancouver General Hospital, British Columbia Cancer Agency, and the University of British Columbia, Vancouver, British Columbia, Canada
2 The Prostate Centre at Vancouver General Hospital, Vancouver Coastal Health Authority, Vancouver, British Columbia, Canada
3 Center for Translational and Applied Genomics, Provincial Health Services Authority & British Columbia Cancer Agency, Vancouver, British Columbia, Canada
Correspondence to:
Dr David G Huntsman, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada; dhuntsma{at}bccancer.bc.ca
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 fluorescence in situ hybridisation (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 (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: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 fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing 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.
Abbreviations: CaP, prostate cancer; FISH, fluorescence in situ hybridisation; PSA, prostate specific antigen; TMA, tissue microarray
Keywords: gene fusion; TMPRSS2:ERG; prostate cancer; FISH
Relevant Article
J. Clin. Pathol. 2007 60: 1185-1186.
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