Title | Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Tomlins 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 |
Journal | Science |
Volume | 310 |
Issue | 5748 |
Pagination | 644-8 |
Date Published | 2005 Oct 28 |
ISSN | 1095-9203 |
Keywords | Androgens, 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 |
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. |
DOI | 10.1126/science.1117679 |
Alternate Journal | Science |
PubMed ID | 16254181 |
Grant List | 5P30 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 |