TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer

Scott A. Tomlins, Rohit Mehra, Daniel R. Rhodes, Lisa R. Smith, Diane Roulston, Beth E. Helgeson, Xuhong Cao, John T. Wei, Mark A. Rubin, Rajal B. Shah, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

359 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3396-3400
Number of pages5
JournalCancer Research
Volume66
Issue number7
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tomlins, S. A., Mehra, R., Rhodes, D. R., Smith, L. R., Roulston, D., Helgeson, B. E., Cao, X., Wei, J. T., Rubin, M. A., Shah, R. B., & Chinnaiyan, A. M. (2006). TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Research, 66(7), 3396-3400. https://doi.org/10.1158/0008-5472.CAN-06-0168