Characterization of TMPRSS2-ETS gene aberrations in androgen-independent metastatic prostate cancer

Rohit Mehra, Scott A. Tomlins, Jianjun Yu, Xuhong Cao, Lei Wang, Anjana Menon, Mark A. Rubin, Kenneth J. Pienta, Rajal B. Shah, Arul M. Chinnaiyan

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206 Scopus citations

Abstract

Recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS transcription factor family members ERG, ETV1, and ETV4 have been identified as a critical event in prostate cancer development. In this study, we characterized the prevalence and diversity of these rearrangements in hormone-refractory metastatic prostate cancer. We used a fluorescence in situ hybridization (FISH) split probe strategy to comprehensively evaluate TMPRSS2-ETS aberrations across 97 nonosseous metastatic sites of prostate cancer from 30 rapid autopsies of men who died of androgen-independent disease. Tissue microarrays were constructed representing multiple metastatic sites from each patient, and split signal FISH probes for TMPRSS2, ERG, ETV1, and ETV4 were used to assess for TMPRSS2-ETS rearrangements. In patients exhibiting these aberrations, multiple sites from an individual case harbored the same gene fusion molecular subtype suggesting clonal expansion of disease. The most common prostate cancer gene fusion, TMPRSS2-ERG, can be generated by the mechanism of interstitial deletion (Edel) about 39% to 60% of the time in clinically localized disease. Interestingly, we observed that all of the androgen-independent metastatic prostate cancer sites harboring TMPRSS2-ERG were associated with Edel. These findings suggest that TMPRSS2-ERG with Edel is an aggressive and, in this study, uniformly lethal molecular subtype of prostate cancer associated with androgen-independent disease.

Original languageEnglish (US)
Pages (from-to)3584-3590
Number of pages7
JournalCancer research
Volume68
Issue number10
DOIs
StatePublished - May 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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 research, 68(10), 3584-3590. https://doi.org/10.1158/0008-5472.CAN-07-6154