title: Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues.
abstract: 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%). RT-PCR 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Jiangling J
authors.initials: JJ
authors.lastname: Tu
authors.forename: Stephen
authors.initials: S
authors.lastname: Rohan
authors.forename: Jean
authors.initials: J
authors.lastname: Kao
authors.forename: Naoki
authors.initials: N
authors.lastname: Kitabayashi
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016612:Paraffin Embedding; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C072312:ERG protein, human; C095239:ETV1 protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; D012313:RNA; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human