These findings indicate a need for prospective studies to evaluate the relationship of TMPRSS2-ERG rearrangement with clinical course of screening-detected prostate cancer in North American men, and a need for the development of noninvasive screening tests to detect TMPRSS2-ERG rearrangement.
In 2005, fusions between the androgen-regulated transmembrane protease serine 2 gene, TMPRSS2, and E twenty-six (ETS) transcription factors were discovered in prostate cancer.
Total RNA from 194 formalin-fixed and paraffin-embedded prostate cancer samples obtained by radical prostatectomy was subjected to reverse-transcriptase polymerase chain reaction to detect the common TMPRSS2:ERG T1-E4 and T1-E5 fusion transcripts and five other non-TMPRSS2:ERG fusion transcripts.
A major breakthrough in prostate cancer was the identification of recurrent fusions between the androgen-regulated gene, TMPRSS2 and the v-ets erythroblastosis virus E26 oncogene homolog, ERG.
Furthermore, within the 26 tumor types assessed for copy number alterations by SNP, the distinct deletion site between TMPRSS2 and ERG (21q22.2-3) was detectable exclusively in prostate cancer.
Although several studies have been done, the clinical utility of TMPRSS2 genetic alterations as biomarkers for prostate carcinoma remains indeterminate.
The identification of the high-frequency TMPRSS2 fusion with ERG and other ETS family genes in prostate cancer highlights the importance of fusion genes in solid tumor development and progression.
Our preliminary study demonstrates that the clinical utility of TMPRSS2-ETS fusion detection as a biomarker and ancillary diagnostic tool for the early diagnosis of prostate cancer is promising, given this approach shows significant high sensitivity and specificity in detection.
Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy.
The TMPRSS2-ERG expressing DuCaP-N cell line represents human prostate cancer prior to endocrine treatment, and its parental DuCaP cell line is a model for CRPC.
This study describes the frequency of ERG rearrangement prostate cancer and three 5 prime (5') gene fusion partners (ie, TMPRSS2, SLC45A3, and NDRG1) in a large prostatectomy cohort.
The results suggest that the up-regulation of TMPRSS2 gene and the down-regulation of KLK11 gene in advanced and more aggressive tumors may open the feasibility of being used as biomarkers distinguishing the tumor aggressiveness as well as novel prognostic indicators for PCa.
Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients.
Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs and was 50-fold more stable than wild-type ETV1.
The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression.
Fusion of the androgen-regulated TMPRSS2 promoter to the ERG oncogene results in constitutive high level expression of ERG which promotes prostate cancer invasion and proliferation.