Journal
MODERN PATHOLOGY
Volume 20, Issue 9, Pages 921-928Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.3800903
Keywords
TMPRSS2; ERG; translocation; microdeletion
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Recurrent gene fusions between TMPRSS2 and ETS family genes have recently been shown to occur at a high frequency in prostate cancer. In this study, we used formalin-fixed paraffin-embedded tissue and evaluated both TMPRSS2-ERG and TMPRSS2-ETV1 fusions by reverse transcription polymerase chain reaction ( RT-PCR) and fluorescence in situ hybridization ( FISH). The results were correlated to overexpression of the downstream ERG and ETV1 sequences. Of 82 cases examined, TMPRSS2-ETV1 fusion was seen in only one case, by FISH. In comparison, TMPRSS2-ERG fusion was documented in 35 cases ( 43%) by either RT-PCR or FISH. Deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion ( 81 vs 19%). RTPCR and FISH results correlated well, with most positive cases resulting in overexpression of downstream ERG sequences. Several TMPRSS2-ERG fusion transcript variants were identified, most of which are predicted to encode truncated ERG proteins. Prostate cancer of Gleason's scores 6 or 7 had more frequent TMPRSS2-ERG fusions than higher-grade tumors, but this difference was not statistically significant ( P= 0.42). On the other hand, mucin-positive carcinomas more often harbor such gene fusions when compared to mucin-negative tumors ( P = 0.004). These morphological correlates, and more importantly the potential correlation of such fusions to clinical outcome and treatment responses, should be further explored.
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