Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer

doi:10.1126/science.1117679

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Science 28 October 2005:
Vol. 310. no. 5748, pp. 644 - 648
DOI: 10.1126/science.1117679

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Research Articles

Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer

Scott A. Tomlins,¹ Daniel R. Rhodes,¹^,2 Sven Perner,⁷^,9 Saravana M. Dhanasekaran,¹ Rohit Mehra,¹ Xiao-Wei Sun,⁷ Sooryanarayana Varambally,¹^,6 Xuhong Cao,¹ Joelle Tchinda,⁷ Rainer Kuefer,¹⁰ Charles Lee,⁷ James E. Montie,³^,5^,6 Rajal B. Shah,¹^,3^,5^,6 Kenneth J. Pienta,³^,4^,5^,6 Mark A. Rubin,⁷^,8 Arul M. Chinnaiyan¹^,2^,3^,5^,6^*

Recurrent chromosomal rearrangements have not been well characterizedin common carcinomas. We used a bioinformatics approach to discovercandidate oncogenic chromosomal aberrations on the basis ofoutlier gene expression. Two ETS transcription factors, ERGand ETV1, were identified as outliers in prostate cancer. Weidentified recurrent gene fusions of the 5' untranslated regionof TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlierexpression. By using fluorescence in situ hybridization, wedemonstrated that 23 of 29 prostate cancer samples harbor rearrangementsin ERG or ETV1. Cell line experiments suggest that the androgen-responsivepromoter elements of TMPRSS2 mediate the overexpression of ETSfamily members in prostate cancer. These results have implicationsin the development of carcinomas and the molecular diagnosisand treatment of prostate cancer.

¹ Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
² Bioinformatics Program, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
³ Department of Urology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
⁴ Department of Internal Medicine, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
⁵ Michigan Urology Center, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
⁶ Comprehensive Cancer Center, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109–0602, USA.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁸ Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
⁹ Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Urology, Faculty of Medicine, University of Ulm, Ulm 89075, Germany.

^* To whom correspondence should be addressed. E-mail: arul{at}umich.edu

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NEWS OF THE WEEK MEDICINE: Fused Genes May Help Explain the Origins of Prostate Cancer: Jean Marx (28 October 2005)
Science 310 (5748), 603a. [DOI: 10.1126/science.310.5748.603a]
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