Recurrent Fusion of <i>TMPRSS2</i> and ETS Transcription Factor Genes in Prostate Cancer

Scott A. Tomlins(University of Michigan), Daniel R. Rhodes(University of Michigan), Sven Perner(University of Michigan), Saravana M. Dhanasekaran(University of Michigan), Rohit Mehra(University of Michigan), Xiao Sun(University of Michigan), Sooryanarayana Varambally(University of Michigan), Xuhong Cao(University of Michigan), Joëlle Tchinda(University of Michigan), Rainer Kuefer(University of Michigan), Charles Lee(University of Michigan), James E. Montie(University of Michigan), Rajal B. Shah(University of Michigan), Kenneth J. Pienta(University of Michigan), Mark A. Rubin(University of Michigan), Arul M. Chinnaiyan(University of Michigan)
Science
October 27, 2005
10.1126/science.1117679
Cited by 3,858

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.

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