PMID- 17637754
OWN - NLM
STAT- MEDLINE
DCOM- 20080215
LR  - 20220414
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 3
DP  - 2008 Jan 10
TI  - Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human 
      prostate cancer.
PG  - 253-63
AB  - New predictive markers for managing prostate cancer are urgently required because 
      of the highly variable natural history of this disease. At the time of diagnosis, 
      Gleason score provides the gold standard for assessing the aggressiveness of 
      prostate cancer. However, the recent discovery of TMPRSS2 fusions to the ERG gene 
      in prostate cancer raises the possibility of using alterations at the ERG locus 
      as additional mechanism-based prognostic indicators. Fluorescence in situ 
      hybridization (FISH) assays were used to assess ERG gene status in a cohort of 
      445 prostate cancers from patients who had been conservatively managed. The FISH 
      assays detected separation of 5' (labelled green) and 3' (labelled red) ERG 
      sequences, which is a consequence of the TMPRSS2-ERG fusion, and additionally 
      identify interstitial deletion of genomic sequences between the tandemly located 
      TMPRSS2 and ERG gene sequences on chromosome 21. Cancers lacking ERG alterations 
      exhibited favourable cause-specific survival (90% survival at 8 years). We 
      identify a novel category of prostate cancers, characterized by duplication of 
      the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of 
      sequences 5' to ERG (called '2+Edel'), which by comparison exhibited extremely 
      poor cause-specific survival (hazard ratio=6.10, 95% confidence ratio=3.33-11.15, 
      P<0.001, 25% survival at 8 years). In multivariate analysis, '2+Edel' provided 
      significant prognostic information (P=0.003) in addition to that provided by 
      Gleason score and prostate-specific antigen level at diagnosis. Other individual 
      categories of ERG alteration were associated with intermediate or good prognosis. 
      We conclude that determination of ERG gene status, including duplication of the 
      fusion of TMPRSS2 to ERG sequences in 2+Edel, allows stratification of prostate 
      cancer into distinct survival categories.
FAU - Attard, G
AU  - Attard G
AD  - Institute of Cancer Research, Male Urological Cancer Research Centre, Surrey, UK.
FAU - Clark, J
AU  - Clark J
FAU - Ambroisine, L
AU  - Ambroisine L
FAU - Fisher, G
AU  - Fisher G
FAU - Kovacs, G
AU  - Kovacs G
FAU - Flohr, P
AU  - Flohr P
FAU - Berney, D
AU  - Berney D
FAU - Foster, C S
AU  - Foster CS
FAU - Fletcher, A
AU  - Fletcher A
FAU - Gerald, W L
AU  - Gerald WL
FAU - Moller, H
AU  - Moller H
FAU - Reuter, V
AU  - Reuter V
FAU - De Bono, J S
AU  - De Bono JS
FAU - Scardino, P
AU  - Scardino P
FAU - Cuzick, J
AU  - Cuzick J
FAU - Cooper, C S
AU  - Cooper CS
CN  - Transatlantic Prostate Group
LA  - eng
GR  - G0501019/MRC_/Medical Research Council/United Kingdom
GR  - P50 CA092629/CA/NCI NIH HHS/United States
GR  - P50 CA092629-07/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070716
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (TMPRSS2 protein, human)
SB  - IM
MH  - Aged
MH  - Base Sequence
MH  - Biomarkers, Tumor/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Prostatic Neoplasms/*diagnosis/*mortality
MH  - Serine Endopeptidases/*genetics
MH  - Survival Analysis
MH  - Trans-Activators/*genetics
MH  - Transcriptional Regulator ERG
PMC - PMC2646890
MID - NIHMS53614
EDAT- 2007/07/20 09:00
MHDA- 2008/02/19 09:00
PMCR- 2009/02/24
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2008/02/19 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
PHST- 2009/02/24 00:00 [pmc-release]
AID - 1210640 [pii]
AID - 10.1038/sj.onc.1210640 [doi]
PST - ppublish
SO  - Oncogene. 2008 Jan 10;27(3):253-63. doi: 10.1038/sj.onc.1210640. Epub 2007 Jul 
      16.