Reid, AHM; Attard, G; Ambroisine, L; Fisher, G; Kovacs, G; Brewer, D; Clark, J; Flohr, P; Edwards, S; Berney, DM; +10 more... Foster, CS; Fletcher, A; Gerald, WL; Møller, H; Reuter, VE; Scardino, PT; Cuzick, J; de Bono, JS; Cooper, CS; Transatlantic Prostate Group; (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 DOI: https://doi.org/10.1038/sj.bjc.6605554
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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.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
PubMed ID | 20104229 |
ISI | 274604900008 |
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