TMPRSS2-ERG Fusion Gene Expression in Prostate Tumor Cells and Its Clinical and Biological Significance in Prostate Cancer Progression

Abstract

TMPRSS2-Ets gene fusions were identified in prostate cancers where the promoter of transmembrane protease, serine 2 (TMPRSS2) fused with coding sequence of the erythroblastosis virus E26 (Ets) gene family members. TMPRSS2 is an androgen responsive transmembrane serine protease. Ets family members are oncogenic transcription factors that contain a highly conserved Ets DNA binding domain and an N-terminal regulatory domain. Fusion of these gene results in androgen dependent transcription of Ets factor in prostate tumor cells. The ERG is the most common fusion partner with TMPRSS2 promoter in prostate cancer patients. The high prevalence of these gene fusions, in particular TMPRSS2-ERG, makes them attractive as potential diagnostic and prognostic indicators, as well as making them a potential target for tailored therapies. This review focuses on the clinical and biological significance of TMPRSS2-ERG fusions and their role in PC development and progression.

ERG rearrangement and protein expression in the progression to castration-resistant prostate cancer

“…Concordantly, in the matched patient cohort, virtually all of the patients retained their ERG status after recurring under ADT. Although earlier reports that had focused on ERG RNA expression analysis or were based on tissues from xenografts had reported controversial prevalence rates in CR PC, 28 our findings are in line with a very recent study by Teng et al . 29 in which the authors observed the ERG expression in 37% of human CR PCs.…”

Identification of Independent Primary Tumors and Intrapulmonary Metastases Using DNA Rearrangements in Non–Small-Cell Lung Cancer

“…In addition, to our knowledge, identical fusions across tumors, even in the highly recurring lung cancer EML4-ALK or prostate TMPRSS2-EFG fusions, have not been reported. [24][25][26][27] The presence of large numbers of shared breakpoints in multiple tumor blocks within single lung cancers further confirms that MP sequencing can detect lineage associations despite tumor heterogeneity. This is an important feature of an approach based on sequencing genomic rearrangements that would not be feasible using the targeted mutation panels that are emerging as an important diagnostic test for lung cancer care.…”

“…21, [24][25][26] Similarly, for the common EML4-ALK translocation observed in approximately 5% of lung adenocarcinomas (ADs), no duplicate breakpoints have been reported in the literature to date, despite overlap in protein products and functional consequence. 27 Furthermore, recent publications used rearrangements to successfully demonstrate lineage of adjacent lepidic and invasive components of lepidic predominant ADs 22 and adjacent Gleason patterns in prostate cancer 21 using next-generation DNA sequencing with a mate-pair (MP) library approach.…”

Diagnostic and Prognostic Scoring System for Prostate Cancer Using Urine and Plasma Biomarkers

“…PCA3 mRNA as a ratio of PSA mRNA in urine has shown improved diagnostic value (area under the receiver operating characteristic curve [AUROC], 66-72%) compared to PSA alone (AUROC, 54-63%), especially when the tested urine was collected post-digital rectal examination (DRE) (Prensner et al, 2012). TMPRSS2-ERG gene fusions are also prevalent in PCa (St John et al, 2012). In 2011, experimental data from post-DRE urinary analysis of TMPRSS2-ERG and PCA3 were combined with sPSA levels to develop a clinically practical multivariate algorithm that improved PCa prediction.…”