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^*

^*Corresponding author for this work

Institute of Pathology

2842 Citations (Scopus)

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
Journal	Science
Volume	310
Issue number	5748
Pages (from-to)	644-648
Number of pages	5
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1117679
Publication status	Published - 28.10.2005

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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.}",

year = "2005",

month = oct,

day = "28",

doi = "10.1126/science.1117679",

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T1 - Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer

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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DO - 10.1126/science.1117679

M3 - Journal articles

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AN - SCOPUS:27344451557

SN - 0036-8075

VL - 310

SP - 644

EP - 648

JO - Science

JF - Science

IS - 5748

ER -

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

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