TY - JOUR
T1 - Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer
AU - Mehra, Rohit
AU - Tomlins, Scott A.
AU - Shen, Ronglai
AU - Nadeem, Owais
AU - Wang, Lei
AU - Wei, John T.
AU - Pienta, Kenneth J.
AU - Ghosh, Debashis
AU - Rubin, Mark A.
AU - Chinnaiyan, Arul M.
AU - Shah, Rajal B.
N1 - Funding Information:
Defense (PC040517 to RM, W81XWH-06-1-0224 to AMC), the National Institutes of Health (Prostate SPORE P50CA69568 to KJP, AMC, and RBS), the Early Detection Research Network (UO1 CA1113913 (PI—Marty Sanda) to AMC and JW). SAT is supported by a Rackham Predoctoral Fellowship. AMC is supported by a Clinical Translational Research Award from the Burroughs Welcome Foundation. SAT is fellow of the Medical Scientist Training Program.
Funding Information:
This work was supported in part by the Prostate Cancer Foundation (to AMC), Department of
PY - 2007/5/30
Y1 - 2007/5/30
N2 - Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3′ end of TMPRSS2 and the 5′ end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5′ and 3′ partners may be involved in gene fusions in prostate cancer.
AB - Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3′ end of TMPRSS2 and the 5′ end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5′ and 3′ partners may be involved in gene fusions in prostate cancer.
KW - Fluorescent in situ hybridization
KW - Gene aberrations
KW - Localized prostate cancer
KW - TMPRSS2, ETS
UR - http://www.scopus.com/inward/record.url?scp=34247363715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247363715&partnerID=8YFLogxK
U2 - 10.1038/modpathol.3800769
DO - 10.1038/modpathol.3800769
M3 - Article
C2 - 17334343
AN - SCOPUS:34247363715
VL - 20
SP - 538
EP - 544
JO - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
SN - 0893-3952
IS - 5
ER -