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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Androgens / metabolism
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Cell Line, Tumor
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DNA-Binding Proteins / genetics*
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Gene Expression Regulation, Neoplastic
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Gene Rearrangement
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Humans
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In Situ Hybridization, Fluorescence
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Male
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Membrane Proteins / genetics*
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Molecular Sequence Data
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Neoplasm Proteins / genetics*
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Oncogene Proteins, Fusion / genetics*
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Polymerase Chain Reaction
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Prostatic Neoplasms / genetics*
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Serine Endopeptidases / genetics*
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Trans-Activators / genetics*
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Transcription Factors / genetics*
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Transcriptional Regulator ERG
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Translocation, Genetic
Substances
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Androgens
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DNA-Binding Proteins
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ERG protein, human
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ETV1 protein, human
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Membrane Proteins
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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Trans-Activators
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Transcription Factors
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Transcriptional Regulator ERG
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Serine Endopeptidases
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TMPRSS3 protein, human
Associated data
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GENBANK/DQ204770
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GENBANK/DQ204771
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GENBANK/DQ204772
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GENBANK/DQ204773