Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer.
Recently, gene fusions between the androgen responsive gene TMPRSS2 and members of the ETS-family of DNA-binding transcription factor genes were found in prostate cancer. Recurrent fusions were identified between the 5'-noncoding region of TMPRSS2 and ERG, or less frequently ETV1 or ETV4, resulting in overexpression of normal or truncated ETS-proteins. Herein, we have analyzed a series of 50 prostate cancer samples for expression of TPRSS2-ERG and TMPRSS2-ETV1 fusion transcripts. RT-PCR analysis revealed TMPRSS2-ERG fusion transcripts in 18 of the 50 tumors (36%). None of the tumors expressed a TMPRSS2-ETV1 fusion. Our findings show that the TMPRSS2-ERG fusion is common in prostate cancer and that the related TMPRSS2-ETV1 fusion is very rare. However, the frequency of ERG-fusions in the present study is somewhat lower than previously observed, indicating heterogeneity with regard to expression of ETS-gene fusions in subsets of prostate cancers. Moreover, clinical follow-up studies showed a clear tendency that fusion-positive tumors were associated with lower Gleason grade and better survival than fusion-negative tumors. Our findings suggest that ERG gene fusions might be of prognostic significance in prostate cancer.
Winnes
Marta
M
Lundberg Laboratory for Cancer Research, Department of Pathology, SE-413 45 Göteborg, Sweden.
Lissbrant
Erik
E
Damber
Jan-Erik
JE
Stenman
Göran
G
D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D014157:Transcription Factors