Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer

Scott A. Tomlins, Daniel R. Rhodes, Sven Perner, Saravana M. Dhanasekaran, Rohit Mehra, Xiao Wei Sun, Sooryanarayana Varambally, Xuhong Cao, Joelle Tchinda, Rainer Kuefer, Charles Lee, James E. Montie, Rajal B. Shah, Kenneth J. Pienta, Mark A. Rubin, Arul M. Chinnaiyan

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Abstract

Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5′ untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)644-648
Number of pages5
JournalScience
Volume310
Issue number5748
DOIs
Publication statusPublished - Oct 28 2005
Externally publishedYes

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Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X. W., ... Chinnaiyan, A. M. (2005). Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 310(5748), 644-648. https://doi.org/10.1126/science.1117679