Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers.
BACKGROUND
Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5' end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3' end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG.


OBJECTIVE
To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs).


METHODS
Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis.


RESULTS
A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed.


CONCLUSIONS
This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.
Rajput
Ashish B
AB
Genetic Pathology Evaluation Centre, Vancouver General Hospital, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada.
Miller
Melinda A
MA
De Luca
Alessandro
A
Boyd
Niki
N
Leung
Sam
S
Hurtado-Coll
Antonio
A
Fazli
Ladan
L
Jones
Edward C
EC
Palmer
Jodie B
JB
Gleave
Martin E
ME
Cox
Michael E
ME
Huntsman
David G
DG
D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D004273:DNA, Neoplasm / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human