This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hermans, K. G. Articles by Trapman, J. Search for Related Content PubMed PubMed Citation Articles by Hermans, K. G. Articles by Trapman, J.

TMPRSS2:ERG Fusion by Translocation or Interstitial Deletion Is Highly Relevant in Androgen-Dependent Prostate Cancer, But Is Bypassed in Late-Stage Androgen Receptor–Negative Prostate Cancer

Departments of ¹ Pathology and ² Urology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, the Netherlands

Requests for reprints: Jan Trapman, Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands. Phone: 31-104087933; Fax: 31-104089487; E-mail: j.trapman{at}erasmusmc.nl.

Recently, a unique fusion between the prostate-specific, androgen-regulated TMPRSS2 gene and the ETS genes ERG, ETV1, or ETV4 has been described in clinical prostate cancer. We investigated mechanisms of expression of four ETS genes, ERG, ETV1, ETV4, and FLI1, in 11 xenografts representing different stages of prostate cancer. All five androgen-dependent xenografts showed as major transcript overexpression of two splice variants of TMPRSS2:ERG, linking TMPRSS2 exon 1 or 2 sequences to ERG exon 4. In one of two androgen-sensitive xenografts, fusion transcripts of TMPRSS2 and ETV1 were detected. Array-based comparative genomic hybridization and interphase fluorescence in situ hybridization indicated both interstitial deletions and translocations as mechanisms of TMPRSS2:ERG gene fusion. Importantly, TMPRSS2 to ERG fusions were also observed in three of four androgen-independent, androgen receptor (AR)–negative xenografts and in two AR-negative clinical prostate cancer specimens; however, the fusion gene was not expressed. In almost all AR-negative tumor samples, overexpression of wild-type ETV4 or FLI1 was detected. Combined, our observations indicate a key role of fusion of TMPRSS2 and ETS genes in most androgen-regulated prostate cancers, which might be bypassed by androgen-independent expression of wild-type ETS factors in late-stage disease. (Cancer Res 2006; 66(22): 10658-63)

This article has been cited by other articles:

				F. H. Jansen, J. Krijgsveld, A. van Rijswijk, G.-J. van den Bemd, M. S. van den Berg, W. M. van Weerden, R. Willemsen, L. J. Dekker, T. M. Luider, and G. Jenster Exosomal Secretion of Cytoplasmic Prostate Cancer Xenograft-derived Proteins Mol. Cell. Proteomics, June 1, 2009; 8(6): 1192 - 1205. [Abstract] [Full Text] [PDF]

				G. Attard, J. F. Swennenhuis, D. Olmos, A. H.M. Reid, E. Vickers, R. A'Hern, R. Levink, F. Coumans, J. Moreira, R. Riisnaes, et al. Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer Cancer Res., April 1, 2009; 69(7): 2912 - 2918. [Abstract] [Full Text] [PDF]

				A. Gopalan, M. A. Leversha, J. M. Satagopan, Q. Zhou, H. A. Al-Ahmadie, S. W. Fine, J. A. Eastham, P. T. Scardino, H. I. Scher, S. K. Tickoo, et al. TMPRSS2-ERG Gene Fusion Is Not Associated with Outcome in Patients Treated by Prostatectomy Cancer Res., February 15, 2009; 69(4): 1400 - 1406. [Abstract] [Full Text] [PDF]

				Q. Lu, E. Nunez, C. Lin, K. Christensen, T. Downs, D. A. Carson, J. Wang-Rodriguez, and Y.-T. Liu A sensitive array-based assay for identifying multiple TMPRSS2:ERG fusion gene variants Nucleic Acids Res., November 1, 2008; 36(20): e130 - e130. [Abstract] [Full Text] [PDF]

				J. Wang, Y. Cai, W. Yu, C. Ren, D. M. Spencer, and M. Ittmann Pleiotropic Biological Activities of Alternatively Spliced TMPRSS2/ERG Fusion Gene Transcripts Cancer Res., October 15, 2008; 68(20): 8516 - 8524. [Abstract] [Full Text] [PDF]

				K. G. Hermans, H. A. van der Korput, R. van Marion, D. J. van de Wijngaart, A. Ziel-van der Made, N. F. Dits, J. L. Boormans, T. H. van der Kwast, H. van Dekken, C. H. Bangma, et al. Truncated ETV1, Fused to Novel Tissue-Specific Genes, and Full-Length ETV1 in Prostate Cancer Cancer Res., September 15, 2008; 68(18): 7541 - 7549. [Abstract] [Full Text] [PDF]

				J. C. Cheville, R. J. Karnes, T. M. Therneau, F. Kosari, J.-M. Munz, L. Tillmans, E. Basal, L. J. Rangel, E. Bergstralh, I. V. Kovtun, et al. Gene Panel Model Predictive of Outcome in Men at High-Risk of Systemic Progression and Death From Prostate Cancer After Radical Retropubic Prostatectomy J. Clin. Oncol., August 20, 2008; 26(24): 3930 - 3936. [Abstract] [Full Text] [PDF]

				G Attard, J E Ang, D Olmos, and J S de Bono Dissecting prostate carcinogenesis through ETS gene rearrangement studies: implications for anticancer drug development J. Clin. Pathol., August 1, 2008; 61(8): 891 - 896. [Abstract] [Full Text] [PDF]

				J. Yan, H. Erdem, R. Li, Y. Cai, G. Ayala, M. Ittmann, L.-y. Yu-Lee, S. Y. Tsai, and M.-J. Tsai Steroid Receptor Coactivator-3/AIB1 Promotes Cell Migration and Invasiveness through Focal Adhesion Turnover and Matrix Metalloproteinase Expression Cancer Res., July 1, 2008; 68(13): 5460 - 5468. [Abstract] [Full Text] [PDF]

				O. R. Saramaki, A. E. Harjula, P. M. Martikainen, R. L. Vessella, T. L.J. Tammela, and T. Visakorpi TMPRSS2:ERG Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis Clin. Cancer Res., June 1, 2008; 14(11): 3395 - 3400. [Abstract] [Full Text] [PDF]

				R. Mehra, S. A. Tomlins, J. Yu, X. Cao, L. Wang, A. Menon, M. A. Rubin, K. J. Pienta, R. B. Shah, and A. M. Chinnaiyan Characterization of TMPRSS2-ETS Gene Aberrations in Androgen-Independent Metastatic Prostate Cancer Cancer Res., May 15, 2008; 68(10): 3584 - 3590. [Abstract] [Full Text] [PDF]

				K. G. Hermans, A. A. Bressers, H. A. van der Korput, N. F. Dits, G. Jenster, and J. Trapman Two Unique Novel Prostate-Specific and Androgen-Regulated Fusion Partners of ETV4 in Prostate Cancer Cancer Res., May 1, 2008; 68(9): 3094 - 3098. [Abstract] [Full Text] [PDF]

				B. E. Helgeson, S. A. Tomlins, N. Shah, B. Laxman, Q. Cao, J. R. Prensner, X. Cao, N. Singla, J. E. Montie, S. Varambally, et al. Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 Gene Fusions in Prostate Cancer Cancer Res., January 1, 2008; 68(1): 73 - 80. [Abstract] [Full Text] [PDF]

				S. Jhavar, A. Reid, J. Clark, Z. Kote-Jarai, T. Christmas, A. Thompson, C. Woodhouse, C. Ogden, C. Fisher, C. Corbishley, et al. Detection of TMPRSS2-ERG Translocations in Human Prostate Cancer by Expression Profiling Using GeneChip Human Exon 1.0 ST Arrays J. Mol. Diagn., January 1, 2008; 10(1): 50 - 57. [Abstract] [Full Text] [PDF]

				A. B Rajput, M. A Miller, A. De Luca, N. Boyd, S. Leung, A. Hurtado-Coll, L. Fazli, E. C Jones, J. B Palmer, M. E Gleave, et al. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers J. Clin. Pathol., November 1, 2007; 60(11): 1238 - 1243. [Abstract] [Full Text] [PDF]

				J. H. Kim, S. M. Dhanasekaran, R. Mehra, S. A. Tomlins, W. Gu, J. Yu, C. Kumar-Sinha, X. Cao, A. Dash, L. Wang, et al. Integrative Analysis of Genomic Aberrations Associated with Prostate Cancer Progression Cancer Res., September 1, 2007; 67(17): 8229 - 8239. [Abstract] [Full Text] [PDF]