期刊
MODERN PATHOLOGY
卷 20, 期 5, 页码 538-544出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.3800769
关键词
localized prostate cancer; TMPRSS2; ETS; fluorescent in situ hybridization; gene aberrations
类别
资金
- NCI NIH HHS [U01 CA1113913, P50CA69568] Funding Source: Medline
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 30 end of TMPRSS2 and the 50 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 50 and 30 partners may be involved in gene fusions in prostate cancer.
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