A three-marker FISH panel detects more genetic aberrations of AR, PTEN and TMPRSS2/ERG in castration-resistant or metastatic prostate cancers than in primary prostate tumors.
TERT-positive cases also had elevated levels of ERG (P=0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors.
To date, there has been no published study describing miRNA associations in prostate tumours that overexpress the ERG oncogene from the TMPRSS2:ERG fusion transcript.
Expert commentary: The new additions to the 2016 WHO tumor classification, which include pathological definition of Intraductal carcinoma of the prostate (IDC-P) and of a new grading system for PCa, as well as identification of molecular markers, such as TMPRSS2-ERG and AR-V7, may pave the way to personalized therapy for patients with prostate tumors.
Utilizing gene expression datasets, from matched normal and prostate tumor epithelial cells, an association of NOTCH transcription factors with <i>ERG</i> expression status was identified, confirming that <i>NOTCH</i> factors are direct transcriptional targets of ERG.
Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients.
In a reverse transcription-polymerase chain reaction (RT-PCR)-based survey of 63 prostate tumor specimens (54 primary and nine lymph node metastases), 44 (70%) cases expressed either the known or novel variant TMPRSS2-ERG fusion, 28 (44%) expressed both, 10 (16%) expressed only the known, and notably six (10%) expressed only the variant isoform fusion.
These novel insights will enhance the understanding of the mechanistic functions of ERG in prostate tumor biology and towards development of early targeted therapeutic strategies for prostate cancer.
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.