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

TitleRecurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
Publication TypeJournal Article
Year of Publication2005
AuthorsTomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun X-W, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM
Date Published2005 Oct 28
KeywordsAndrogens, Cell Line, Tumor, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Male, Membrane Proteins, Molecular Sequence Data, Neoplasm Proteins, Oncogene Proteins, Fusion, Polymerase Chain Reaction, Prostatic Neoplasms, Serine Endopeptidases, Trans-Activators, Transcription Factors, Translocation, Genetic

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.

Alternate JournalScience
PubMed ID16254181
Grant List5P30 CA46592 / CA / NCI NIH HHS / United States
P50CA69568 / CA / NCI NIH HHS / United States
R01 CA97063 / CA / NCI NIH HHS / United States
R01AG21404 / AG / NIA NIH HHS / United States
UO1 CA111275-01 / CA / NCI NIH HHS / United States