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., Moller, H., Reuter, V. E., Scardino, P. T., Cuzick, J., de Bono, J. S., Cooper, C. S., Transatlantic Prostate Grp, [Group Author] (2010) Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. BRITISH JOURNAL OF CANCER, 102 (4). pp. 678-684. ISSN 0007-0920

Full text not available from this repository.

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. British Journal of Cancer (2010) 102, 678-684. doi:10.1038/sj.bjc.6605554 www.bjcancer.com Published online 26 January 2010 (C) 2010 Cancer Research UK

Item Type:	Article
Authors (ICR Faculty only):	Cooper, Colin and De-Bono, Johann
All 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., Moller, H., Reuter, V. E., Scardino, P. T., Cuzick, J., de Bono, J. S., Cooper, C. S., Transatlantic Prostate Grp, [Group Author]
Uncontrolled Keywords:	ERG/ETV1 gene rearrangements; fluorescence in situ hybridisation; PTEN gene loss; prostate cancer; survival;GENOMIC DELETION; FISH ANALYSIS; FUSION; EXPRESSION; TMPRSS2-ERG; OVEREXPRESSION; HETEROGENEITY; REARRANGEMENT; RECURRENCE; ACTIVATION
Funding Acknowledgement:	National Cancer Research Institute ; Prostate Cancer Charity ; Grand Charity of Freemasons ; Rosetrees Trust ; Bob Champion Cancer Trust ; Royal Marsden Clinical Research Fund ; Orchid Appeal ; Cancer Research UK ; Medical Research Council ; Prostate Cancer Research Foundation
Funding Text:	This work was funded by the National Cancer Research Institute, The Prostate Cancer Charity, The Grand Charity of Freemasons, The Rosetrees Trust, The Bob Champion Cancer Trust and The Royal Marsden Clinical Research Fund. Dr DM Berney is supported by The Orchid Appeal. Dr JS de Bono was supported by Cancer Research UK, the Medical Research Council, and Prostate Cancer Research Foundation. Dr G Attard is a Prostate Cancer Foundation Young Investigator and Drs Reid and Attard have received Cancer Research UK funding.
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers Closed research groups > Cell Transformation ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Users 10 not found.
Date Deposited:	05 Mar 2010 10:23
Last Modified:	12 May 2017 15:51
URI:	http://publications.icr.ac.uk/id/eprint/9357

Actions (login required)

View Item