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.
authors.affiliation: The Institute of Cancer Research, Male Urological Cancer Research Centre, Surrey, UK.
authors.forename: A H M
authors.initials: AH
authors.lastname: Reid
authors.forename: G
authors.initials: G
authors.lastname: Attard
authors.forename: L
authors.initials: L
authors.lastname: Ambroisine
authors.forename: G
authors.initials: G
authors.lastname: Fisher
authors.forename: G
authors.initials: G
authors.lastname: Kovacs
authors.forename: D
authors.initials: D
authors.lastname: Brewer
authors.forename: J
authors.initials: J
authors.lastname: Clark
authors.forename: P
authors.initials: P
authors.lastname: Flohr
authors.forename: S
authors.initials: S
authors.lastname: Edwards
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
authors.forename: A
authors.initials: A
authors.lastname: Fletcher
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: H
authors.initials: H
authors.lastname: Møller
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
authors.forename: P T
authors.initials: PT
authors.lastname: Scardino
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
authors.forename: C S
authors.initials: CS
authors.lastname: Cooper
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human