RT Journal Article
SR Electronic
T1 Frequency of the <em>TMPRSS2:ERG</em> gene fusion is increased in moderate to poorly differentiated prostate cancers
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 1238
OP 1243
DO 10.1136/jcp.2006.043810
VO 60
IS 11
A1 Rajput, Ashish B
A1 Miller, Melinda A
A1 De Luca, Alessandro
A1 Boyd, Niki
A1 Leung, Sam
A1 Hurtado-Coll, Antonio
A1 Fazli, Ladan
A1 Jones, Edward C
A1 Palmer, Jodie B
A1 Gleave, Martin E
A1 Cox, Michael E
A1 Huntsman, David G
YR 2007
UL http://jcp.bmj.com/content/60/11/1238.abstract
AB 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.