ORIGINAL ARTICLES

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

Ashish B Rajput¹, Melinda A Miller³, Alessandro De Luca³, Niki Boyd³, Sam Leung¹, Antonio Hurtado-Coll², Ladan Fazli², Edward C Jones², Jodie B Palmer², Martin E Gleave², Michael E Cox² and David G Huntsman¹

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

TMPRSS2-ETS fusion prostate cancer: biological and clinical implications

Francesca Demichelis and Mark A Rubin
J. Clin. Pathol. 2007 60: 1185-1186. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Hofer, M. D., Kuefer, R., Maier, C., Herkommer, K., Perner, S., Demichelis, F., Paiss, T., Vogel, W., Rubin, M. A., Hoegel, J. (2009). Genome-Wide Linkage Analysis of TMPRSS2-ERG Fusion in Familial Prostate Cancer. Cancer Res. 69: 640-646 [Abstract] [Full Text]  
• Lu, Q., Nunez, E., Lin, C., Christensen, K., Downs, T., Carson, D. A., Wang-Rodriguez, J., Liu, Y.-T. (2008). A sensitive array-based assay for identifying multiple TMPRSS2:ERG fusion gene variants. Nucleic Acids Res 36: e130-e130 [Abstract] [Full Text]  
• Wang, J., Cai, Y., Yu, W., Ren, C., Spencer, D. M., Ittmann, M. (2008). Pleiotropic Biological Activities of Alternatively Spliced TMPRSS2/ERG Fusion Gene Transcripts. Cancer Res. 68: 8516-8524 [Abstract] [Full Text]  
• Han, B., Mehra, R., Dhanasekaran, S. M., Yu, J., Menon, A., Lonigro, R. J., Wang, X., Gong, Y., Wang, L., Shankar, S., Laxman, B., Shah, R. B., Varambally, S., Palanisamy, N., Tomlins, S. A., Kumar-Sinha, C., Chinnaiyan, A. M. (2008). A Fluorescence In situ Hybridization Screen for E26 Transformation-Specific Aberrations: Identification of DDX5-ETV4 Fusion Protein in Prostate Cancer. Cancer Res. 68: 7629-7637 [Abstract] [Full Text]  
• Cheville, J. C., Karnes, R. J., Therneau, T. M., Kosari, F., Munz, J.-M., Tillmans, L., Basal, E., Rangel, L. J., Bergstralh, E., Kovtun, I. V., Savci-Heijink, C.D., Klee, E. W., Vasmatzis, G. (2008). Gene Panel Model Predictive of Outcome in Men at High-Risk of Systemic Progression and Death From Prostate Cancer After Radical Retropubic Prostatectomy. JCO 26: 3930-3936 [Abstract] [Full Text]  
• Hu, Y., Dobi, A., Sreenath, T., Cook, C., Tadase, A. Y., Ravindranath, L., Cullen, J., Furusato, B., Chen, Y., Thangapazham, R. L., Mohamed, A., Sun, C., Sesterhenn, I. A., McLeod, D. G., Petrovics, G., Srivastava, S. (2008). Delineation of TMPRSS2-ERG Splice Variants in Prostate Cancer. Clin. Cancer Res. 14: 4719-4725 [Abstract] [Full Text]  
• Attard, G, Ang, J E, Olmos, D, de Bono, J S (2008). Dissecting prostate carcinogenesis through ETS gene rearrangement studies: implications for anticancer drug development. J. Clin. Pathol. 61: 891-896 [Abstract] [Full Text]  
• Mosquera, J.-M., Perner, S., Genega, E. M., Sanda, M., Hofer, M. D., Mertz, K. D., Paris, P. L., Simko, J., Bismar, T. A., Ayala, G., Shah, R. B., Loda, M., Rubin, M. A. (2008). Characterization of TMPRSS2-ERG Fusion High-Grade Prostatic Intraepithelial Neoplasia and Potential Clinical Implications. Clin. Cancer Res. 14: 3380-3385 [Abstract] [Full Text]  
• Saramaki, O. R., Harjula, A. E., Martikainen, P. M., Vessella, R. L., Tammela, T. L.J., Visakorpi, T. (2008). TMPRSS2:ERG Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis. Clin. Cancer Res. 14: 3395-3400 [Abstract] [Full Text]  
• Mehra, R., Tomlins, S. A., Yu, J., Cao, X., Wang, L., Menon, A., Rubin, M. A., Pienta, K. J., Shah, R. B., Chinnaiyan, A. M. (2008). Characterization of TMPRSS2-ETS Gene Aberrations in Androgen-Independent Metastatic Prostate Cancer. Cancer Res. 68: 3584-3590 [Abstract] [Full Text]  
• Demichelis, F., Rubin, M. A (2007). TMPRSS2-ETS fusion prostate cancer: biological and clinical implications. J. Clin. Pathol. 60: 1185-1186 [Full Text]