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

Scott A. Tomlins; Daniel R. Rhodes; Sven Perner; Saravana M. Dhanasekaran; Rohit Mehra; Xiao Wei Sun; Sooryanarayana Varambally; Xuhong Cao; Joelle Tchinda; Rainer Kuefer; Charles Lee; James E. Montie; Rajal B. Shah; Kenneth J. Pienta; Mark A. Rubin; Arul M. Chinnaiyan

doi:10.1126/science.1117679

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

Scott A. Tomlins, Daniel R. Rhodes, Sven Perner, Saravana M. Dhanasekaran, Rohit Mehra, Xiao Wei Sun, Sooryanarayana Varambally, Xuhong Cao, Joelle Tchinda, Rainer Kuefer, Charles Lee, James E. Montie, Rajal B. Shah, Kenneth J. Pienta, Mark A. Rubin, Arul M. Chinnaiyan

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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.

Original language	English (US)
Pages (from-to)	644-648
Number of pages	5
Journal	Science
Volume	310
Issue number	5748
DOIs	https://doi.org/10.1126/science.1117679
State	Published - Oct 28 2005
Externally published	Yes

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Tomlins, S. A., Rhodes, D. R., Perner, S., Dhanasekaran, S. M., Mehra, R., Sun, X. W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., Lee, C., Montie, J. E., Shah, R. B., Pienta, K. J., Rubin, M. A., & Chinnaiyan, A. M. (2005). Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 310(5748), 644-648. https://doi.org/10.1126/science.1117679

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title = "Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer",

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.",

author = "Tomlins, {Scott A.} and Rhodes, {Daniel R.} and Sven Perner and Dhanasekaran, {Saravana M.} and Rohit Mehra and Sun, {Xiao Wei} and Sooryanarayana Varambally and Xuhong Cao and Joelle Tchinda and Rainer Kuefer and Charles Lee and Montie, {James E.} and Shah, {Rajal B.} and Pienta, {Kenneth J.} and Rubin, {Mark A.} and Chinnaiyan, {Arul M.}",

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AU - Tomlins, Scott A.

AU - Rhodes, Daniel R.

AU - Perner, Sven

AU - Dhanasekaran, Saravana M.

AU - Mehra, Rohit

AU - Sun, Xiao Wei

AU - Varambally, Sooryanarayana

AU - Cao, Xuhong

AU - Tchinda, Joelle

AU - Kuefer, Rainer

AU - Lee, Charles

AU - Montie, James E.

AU - Shah, Rajal B.

AU - Pienta, Kenneth J.

AU - Rubin, Mark A.

AU - Chinnaiyan, Arul M.

PY - 2005/10/28

Y1 - 2005/10/28

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.

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

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