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

by: SA Tomlins, DR Rhodes, S Perner, SM Dhanasekaran, R Mehra, XW Sun, S Varambally, X Cao, J Tchinda, R Kuefer, C Lee, JE Montie, RB Shah, KJ Pienta, MA Rubin, AM Chinnaiyan

Science, Vol. 310, No. 5748. (28 October 2005), pp. 644-648.

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The authors have used a method called COPA, for Cancer Outlier Profile Analysis. This method does a median centering, and a median absolute deviation normalization for each gene. Then for each gene, the 75th, 90th, 95th percentile are calculated. The genes are then sorted by these values, which recapitulate the tendencies of genes to be over-expressed in a subset of samples. Simple but apparently efficient: they find that ERG/ETV1 genes in prostate cancer score high using this approach. The over-expression of these two genes is then explained by a recurrent fusion with TMPRSS2, a highly expressed gene in prostate (and androgen-regulated).

Reviewed by oelemento - 2008-05-04 19:26:19

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bioinformatics, cancer, copa, ets, fusion, fusion-genes, medicine, molbio, mutations, no-tag, prostate_cancer, prostate-cancer, protein

摘要

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.

@article{citeulike:384555, 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.}, address = {Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602, USA.}, author = {Tomlins, S. A. and Rhodes, D. R. and Perner, S. and Dhanasekaran, S. M. and Mehra, R. and Sun, X. W. and Varambally, S. and Cao, X. and Tchinda, J. and Kuefer, R. and Lee, C. and Montie, J. E. and Shah, R. B. and Pienta, K. J. and Rubin, M. A. and Chinnaiyan, A. M. }, citeulike-article-id = {384555}, doi = {http://dx.doi.org/10.1126/science.1117679}, issn = {1095-9203}, journal = {Science}, month = {October}, number = {5748}, pages = {644--648}, posted-at = {2008-06-30 15:27:25}, priority = {2}, title = {Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.}, url = {http://dx.doi.org/10.1126/science.1117679}, volume = {310}, year = {2005} }

RIS record

TY - JOUR ID - citeulike:384555 L3 - citeulike-article-id:384555 N2 - 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. IS - 5748 JF - Science SN - 1095-9203 AD - Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109-0602, USA. EP - 648 TI - Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. VL - 310 SP - 644 AU - Tomlins, SA AU - Rhodes, DR AU - Perner, S AU - Dhanasekaran, SM AU - Mehra, R AU - Sun, XW AU - Varambally, S AU - Cao, X AU - Tchinda, J AU - Kuefer, R AU - Lee, C AU - Montie, JE AU - Shah, RB AU - Pienta, KJ AU - Rubin, MA AU - Chinnaiyan, AM PY - 2005/10/28/ UR - http://dx.doi.org/10.1126/science.1117679 ER -

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