Molecular genetic analyses of the TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in 50 cases of prostate cancer

Abstract

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.

Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome

“…19 Evidence of specific TMPRSS2:ERG isoforms were also described to be associated with high levels of fusion mRNA expression and early biochemical recurrence following radical prostatectomy. 22 However, there are a number of conflicting studies 29,30 about the prognostic importance of the gene fusion; so the clinical significance of TMPRSS2:ERG fusions remains to be clarified.…”

Urine markers in monitoring for prostate cancer

“…65 Similar findings have been reported in another study with a clear tendency for fusion-positive tumors to be associated with lower Gleason grade and better survival than fusion-negative tumors. 66 No significant association was found between TMPRSS2/ERG status and tumor stage, Gleason grade or recurrence-free survival in another study. 55 The reason of such controversial results could be small sample size in almost all studies listed above.…”

Serum Sarcosine and PSA Levels in Patients With Prostate Cancer in Sokoto, Nigeria.

“…Adjunctive measurements considering the rate of PSA changes with time, the ratios of free and proteinbound PSA, and the relationship of PSA to prostate size have improved performance characteristics in some settings 15 . Several nomograms combining PSA with other clinical variables have also been developed to improve prognostic value beyond that of individual tests 16 Clinical significance of these PSA derivatives has been reported elsewhere. Serum PSA circulates in either an unbound "free" form or bound to one of several proteins, most frequently alpha-1-antichymotrypsin (ACT) 17 .…”