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ETS Gene Fusions in Prostate Cancer: From Discovery to Daily Clinical Practice

Tomlins, Scott A.; Bjartell, Anders LU ; Chinnaiyan, Arul M.; Jenster, Guido; Nam, Robert K.; Rubin, Mark A. and Schalken, Jack A. (2009) In European Urology 56(2). p.275-286
Abstract
Context. In 2005, fusions between the androgen-regulated transmembrane protease serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were discovered in prostate cancer. Objective: To review advances in our understanding of ETS gene fusions, focusing on challenges affecting translation to clinical application. Evidence acquisition: The PubMed database was searched for reports on ETS fusions in prostate cancer. Evidence synthesis: Since the discovery of ETS fusions, novel 5' and 3' fusion partners and multiple splice isoforms have been reported. The most common fusion, TMPRSS2:ERG, is present in approximately 50% of prostate-specific antigen (PSA)-screened localized prostate cancers and in 15-35% of population-based cohorts.... (More)
Context. In 2005, fusions between the androgen-regulated transmembrane protease serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were discovered in prostate cancer. Objective: To review advances in our understanding of ETS gene fusions, focusing on challenges affecting translation to clinical application. Evidence acquisition: The PubMed database was searched for reports on ETS fusions in prostate cancer. Evidence synthesis: Since the discovery of ETS fusions, novel 5' and 3' fusion partners and multiple splice isoforms have been reported. The most common fusion, TMPRSS2:ERG, is present in approximately 50% of prostate-specific antigen (PSA)-screened localized prostate cancers and in 15-35% of population-based cohorts. ETS fusions can be detected noninvasively in the urine of men with prostate cancer, with a specificity rate in PSA-screened cohorts of >90%. Reports from untreated population-based cohorts suggest an association between ETS fusions and cancer-specific death and metastatic spread. In retrospective prostatectomy cohorts, conflicting results have been published regarding associations between ETS fusions and cancer aggressiveness. In addition to serving as a potential biomarker, tissue and functional studies suggest a specific role for ETS fusions in the transition to carcinoma. Finally, recent results suggest that the 5' and 3' ends of ETS fusions as well as downstream targets may be targeted therapeutically. Conclusions: Recent studies suggest that the first clinical applications of ETS fusions are likely to be in noninvasive detection of prostate cancer and in aiding with difficult diagnostic cases. Additional studies are needed to clarify the association between gene fusions and cancer aggressiveness, particularly those studies that take into account the multifocal and heterogeneous nature of localized prostate cancer. Multiple promising strategies have been identified to potentially target ETS fusions. Together, these results suggest that ETS fusions will affect multiple aspects of prostate cancer diagnosis and management. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Early diagnosis, TMPRSS2, Prostate cancer, ETS gene fusions
in
European Urology
volume
56
issue
2
pages
275 - 286
publisher
Elsevier
external identifiers
  • wos:000268527600011
  • scopus:67649425225
ISSN
1873-7560
DOI
10.1016/j.eururo.2009.04.036
language
English
LU publication?
yes
id
0ed690fd-c728-430b-82df-d5b037fd760f (old id 1460012)
date added to LUP
2009-08-31 11:05:10
date last changed
2017-12-10 04:14:02
@article{0ed690fd-c728-430b-82df-d5b037fd760f,
  abstract     = {Context. In 2005, fusions between the androgen-regulated transmembrane protease serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were discovered in prostate cancer. Objective: To review advances in our understanding of ETS gene fusions, focusing on challenges affecting translation to clinical application. Evidence acquisition: The PubMed database was searched for reports on ETS fusions in prostate cancer. Evidence synthesis: Since the discovery of ETS fusions, novel 5' and 3' fusion partners and multiple splice isoforms have been reported. The most common fusion, TMPRSS2:ERG, is present in approximately 50% of prostate-specific antigen (PSA)-screened localized prostate cancers and in 15-35% of population-based cohorts. ETS fusions can be detected noninvasively in the urine of men with prostate cancer, with a specificity rate in PSA-screened cohorts of >90%. Reports from untreated population-based cohorts suggest an association between ETS fusions and cancer-specific death and metastatic spread. In retrospective prostatectomy cohorts, conflicting results have been published regarding associations between ETS fusions and cancer aggressiveness. In addition to serving as a potential biomarker, tissue and functional studies suggest a specific role for ETS fusions in the transition to carcinoma. Finally, recent results suggest that the 5' and 3' ends of ETS fusions as well as downstream targets may be targeted therapeutically. Conclusions: Recent studies suggest that the first clinical applications of ETS fusions are likely to be in noninvasive detection of prostate cancer and in aiding with difficult diagnostic cases. Additional studies are needed to clarify the association between gene fusions and cancer aggressiveness, particularly those studies that take into account the multifocal and heterogeneous nature of localized prostate cancer. Multiple promising strategies have been identified to potentially target ETS fusions. Together, these results suggest that ETS fusions will affect multiple aspects of prostate cancer diagnosis and management. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.},
  author       = {Tomlins, Scott A. and Bjartell, Anders and Chinnaiyan, Arul M. and Jenster, Guido and Nam, Robert K. and Rubin, Mark A. and Schalken, Jack A.},
  issn         = {1873-7560},
  keyword      = {Early diagnosis,TMPRSS2,Prostate cancer,ETS gene fusions},
  language     = {eng},
  number       = {2},
  pages        = {275--286},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {ETS Gene Fusions in Prostate Cancer: From Discovery to Daily Clinical Practice},
  url          = {http://dx.doi.org/10.1016/j.eururo.2009.04.036},
  volume       = {56},
  year         = {2009},
}