Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer Journal Article

   

Authors:	Reid, A. H. M.; Attard, G.; Ambroisine, L.; Fisher, G.; Kovacs, G.; Brewer, D.; Clark, J.; Flohr, P.; Edwards, S.; Berney, D. M.; Foster, C. S.; Fletcher, A.; Gerald, W. L.; Møller, H.; Reuter, V. E.; Scardino, P. T.; Cuzick, J.; de Bono, J. S.; Cooper, C. S.
Article Title:	Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer
Abstract:	Background: The discovery of ERG/ETV1 gene rearrangements and PTEN gene loss warrants investigation in a mechanism-based prognostic classification of prostate cancer (PCa). The study objective was to evaluate the potential clinical significance and natural history of different disease categories by combining ERG/ETV1 gene rearrangements and PTEN gene loss status. Methods:We utilised fluorescence in situ hybridisation (FISH) assays to detect PTEN gene loss and ERG/ETV1 gene rearrangements in 308 conservatively managed PCa patients with survival outcome data.results: ERG/ETV1 gene rearrangements alone and PTEN gene loss alone both failed to show a link to survival in multivariate analyses. However, there was a strong interaction between ERG/ETV1 gene rearrangements and PTEN gene loss (P<0.001). The largest subgroup of patients (54%), lacking both PTEN gene loss and ERG/ETV1 gene rearrangements comprised a good prognosis population exhibiting favourable cancer-specific survival (85.5% alive at 11 years). The presence of PTEN gene loss in the absence of ERG/ETV1 gene rearrangements identified a patient population (6%) with poorer cancer-specific survival that was highly significant (HR=4.87, P<0.001 in multivariate analysis, 13.7% survival at 11 years) when compared with the good prognosis group. ERG/ETV1 gene rearrangements and PTEN gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved. Conclusions Our data suggest that FISH studies of PTEN gene loss and ERG/ETV1 gene rearrangements could be pursued for patient stratification, selection and hypothesis-generating subgroup analyses in future PCa clinical trials and potentially in patient management. © 2010 Cancer Research UK All rights reserved.
Keywords:	survival; cancer survival; controlled study; human tissue; aged; middle aged; survival analysis; retrospective studies; major clinical study; dna-binding proteins; prospective study; genetic analysis; in situ hybridization, fluorescence; cohort studies; models, biological; gene locus; genetic association; risk factors; prediction; cancer mortality; transcription factors; prostate cancer; prostatic neoplasms; cause of death; fluorescence in situ hybridization; gene rearrangement; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; transcription factor erg; carcinoma; gene loss; tissue array analysis; trans-activators; dna mutational analysis; transcription factor er81; genetic loci; erg/etv1 gene rearrangements; fluorescence in situ hybridisation; pten gene loss
Journal Title:	British Journal of Cancer
Volume:	102
Issue:	4
ISSN:	0007-0920
Publisher:	Nature Publishing Group
Date Published:	2010-02-16
Start Page:	678
End Page:	684
Language:	English
DOI:	10.1038/sj.bjc.6605554
PUBMED:	20104229
PROVIDER:	scopus
PMCID:	PMC2837564
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-76949106361&partnerID=40&md5=02e5daa6f8c179d062d3ed9d4dac98a6
Notes:	--- - "Cited By (since 1996): 7" - "Export Date: 20 April 2011" - "CODEN: BJCAA" - "Source: Scopus"

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