TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort.
The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high ets-related [corrected] gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.
Demichelis
F
F
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115-6110, USA.
Fall
K
K
Perner
S
S
Andrén
O
O
Schmidt
F
F
Setlur
S R
SR
Hoshida
Y
Y
Mosquera
J-M
JM
Pawitan
Y
Y
Lee
C
C
Adami
H-O
HO
Mucci
L A
LA
Kantoff
P W
PW
Andersson
S-O
SO
Chinnaiyan
A M
AM
Johansson
J-E
JE
Rubin
M A
MA
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human