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ETS gene fusions in prostate cancer: from discovery to daily clinical practice.

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.

journal_name

Eur Urol

journal_title

European urology

authors

Tomlins SA,Bjartell A,Chinnaiyan AM,Jenster G,Nam RK,Rubin MA,Schalken JA

doi

10.1016/j.eururo.2009.04.036

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

275-86

issue

eissn

0302-2838

issn

1873-7560

pii

S0302-2838(09)00432-1

journal_volume

pub_type

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ETS gene fusions in prostate cancer: from discovery to daily clinical practice.