DOI: 10.1126/science.1117679. Recurrent Fusion of <i>TMPRSS2</i> and ETS Transcription Factor Genes in Prostate Cancer

Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer

10.1126/science.1117679

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

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), 644â648.

Authors 16

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

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We thank D. Roulston and E. Fearon for helpful discussions D. Robins and K. Burnstein for the PC3+AR cells and R. Desphande and C. Creighton for technical assistance. Supported by the Early Detection Research Network Biomarker Developmental Lab UO1 CA111275-01 (to A.M.C.); NIH Prostate specialized program of research excellence (SPORE) P50CA69568 (to K.J.P) RO1 CA97063 (to A.M.C.) and R01AG21404 (to M.A.R.); American Cancer Society RSG-02-179-MGO (to A.M.C.); Department of Defense (PC040517 to R.M. and PC020322 to A.M.C.); and the Cancer Center Bioinformatics Core (support grant 5P30 CA46592). D.R.R. is supported by the Cancer Biology Training Program. K.J.P. is an American Cancer Society Clinical Research Professor. A.M.C. is a Pew Biomedical Scholar and S.A.T. and D.R.R. are Fellows of the Medical Scientist Training Program. Nucleotide sequences for the TMPRSS2:ETS fusions have been deposited at GenBank with accession numbers DQ204770 to DQ04773.

Dates

Type	When
Created	19 years, 10 months ago (Oct. 27, 2005, 6:38 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 8:54 p.m.)
Indexed	2 days, 1 hour ago (Aug. 31, 2025, 6:27 a.m.)
Issued	19 years, 10 months ago (Oct. 28, 2005)
Published	19 years, 10 months ago (Oct. 28, 2005)
Published Print	19 years, 10 months ago (Oct. 28, 2005)

Funders 0

None

BibTeX

@article{Tomlins_2005, title={Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer}, volume={310}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1117679}, DOI={10.1126/science.1117679}, number={5748}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Tomlins, Scott A. and Rhodes, Daniel R. and Perner, Sven and Dhanasekaran, Saravana M. and Mehra, Rohit and Sun, Xiao-Wei and Varambally, Sooryanarayana and Cao, Xuhong and Tchinda, Joelle and Kuefer, Rainer and Lee, Charles and Montie, James E. and Shah, Rajal B. and Pienta, Kenneth J. and Rubin, Mark A. and Chinnaiyan, Arul M.}, year={2005}, month=oct, pages={644–648} }

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