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[Cancer Research 66, 3396-3400, April 1, 2006]
© 2006 American Association for Cancer Research

Priority Reports

TMPRSS2:ETV4 Gene Fusions Define a Third Molecular Subtype of Prostate Cancer

Scott A. Tomlins1, Rohit Mehra1, Daniel R. Rhodes1,3, Lisa R. Smith1, Diane Roulston1, Beth E. Helgeson1, Xuhong Cao1, John T. Wei2,4,5, Mark A. Rubin6,7, Rajal B. Shah1,2,4,5 and Arul M. Chinnaiyan1,2,3,4,5

Departments of 1 Pathology and 2 Urology, 3 Program of Bioinformatics, 4 Michigan Urology Center, and the 5 Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan and 6 Department of Pathology, Brigham and Women's Hospital, and 7 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Arul M. Chinnaiyan, Departments of Pathology and Urology, University of Michigan Medical School, University of Michigan, 1301 Catherine Street, MSI 4237, Ann Arbor, MI 48109-0602. Phone: 734-647-8153; Fax: 734-936-7361; E-mail: arul{at}umich.edu.

Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. Here, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified marked overexpression of ETV4 in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4 (17q21) loci are fused in this case. This result defines a third molecular subtype of prostate cancer and supports the hypothesis that dysregulation of ETS family members through fusions with TMRPSS2 may be an initiating event in prostate cancer development. (Cancer Res 2006; 66(7): 3396-400)




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