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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 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.
1 Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, USA.
2 Bioinformatics Program, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, USA.
3 Department of Urology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, USA.
4 Department of Internal Medicine, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, USA.
5 Michigan Urology Center, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, USA.
6 Comprehensive Cancer Center, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 481090602, 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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