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J Clin Pathol 2007;60:1238-1243 doi:10.1136/jcp.2006.043810
  • Original article

Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers

  1. Ashish B Rajput1,
  2. Melinda A Miller3,
  3. Alessandro De Luca3,
  4. Niki Boyd3,
  5. Sam Leung1,
  6. Antonio Hurtado-Coll2,
  7. Ladan Fazli2,
  8. Edward C Jones2,
  9. Jodie B Palmer2,
  10. Martin E Gleave2,
  11. Michael E Cox2,
  12. David G Huntsman1
  1. 1
    Genetic Pathology Evaluation Centre, Vancouver General Hospital, British Columbia Cancer Agency, and the University of British Columbia, Vancouver, British Columbia, Canada
  2. 2
    The Prostate Centre at Vancouver General Hospital, Vancouver Coastal Health Authority, Vancouver, British Columbia, Canada
  3. 3
    Center for Translational and Applied Genomics, Provincial Health Services Authority & British Columbia Cancer Agency, Vancouver, British Columbia, Canada
  1. Dr David G Huntsman, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada; dhuntsma{at}bccancer.bc.ca
  • Accepted 4 January 2007
  • Published Online First 26 January 2007

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 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.

Footnotes

  • Funding: This work was supported in part by the Canadian Institutes of Health Research Strategic Training Program (Grant STP-53912). The Genetic Pathology Evaluation Centre is supported by an educational grant from Sanofi-Aventis, Canada. D Huntsman and M Cox are Michael Smith Health Foundation for Research Scholars. A De Luca is a recipient of the Michael Smith Health Foundation for Research post-doctoral award and J Palmer is supported in part by the British Columbia Foundation for Prostate Cancer Research.

  • Competing interests: None declared.

  • Abbreviations:
    CaP
    prostate cancer
    FISH
    fluorescence in situ hybridisation
    PSA
    prostate specific antigen
    TMA
    tissue microarray

Responses to this article

  • TMPRSS2-ERG in Localized Parostate Cancer
    • Tarek A. Bismar
    J Clin Pathol published online November 7, 2007

This Article

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    1. jcp.2006.043810v1
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