This study, analysing laser microdissected paired benign and malignant prostate epithelial cells from prostate cancer (CaP) patients (n=114; 228 specimen) by GeneChip and quantitative real-time RT-PCR, identifies ETS-related gene (ERG), a member of the ETS transcription factor family, as the most frequently overexpressed proto-oncogene in the transcriptome of malignant prostate epithelial cells.
In summary, our data indicate that the TMPRSS2:ERG translocation is common in advanced prostate cancer and occurs by virtue of unbalanced genomic rearrangements.
TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer.
Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement.
These results demonstrate that TMPRSS2:ERG gene fusions can be detected in the urine of patients with prostate cancer and support larger studies on prospective cohorts for noninvasive detection of prostate cancer.
The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement.
In this study, we have demonstrated interfocal heterogeneity and intrafocal homogeneity for TMPRSS2-ERG fusion in prostate cancer with multiple tumors.
In this report, we used for the first time the combination of the prostate cancer-specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.
We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors.
Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5' and 3' partners may be involved in gene fusions in prostate cancer.
Five morphological features were associated with TMPRSS2-ERG fusionprostate cancer: blue-tinged mucin, cribriform growth pattern, macronucleoli, intraductal tumour spread, and signet-ring cell features, all with p-values < 0.05.
The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer.
We assayed for the presence of the TMPRSS2:ERG gene fusion product among 26 patients who underwent surgery for clinically localized prostate cancer using RT-PCR and direct DNA sequencing, and evaluated its prognostic significance.
Nonetheless, the discovery of a novel variant TMPRSS2 isoform-ERG fusion adds to the characterization of ETS-family rearrangements in prostate cancer, and has important implications for the accurate molecular diagnosis of TMPRSS2-ETS fusions.
The frequency of the TMPRSS2:ERG fusion in clinical prostate cancer (n = 253) on tissue microarrays was assessed by three-color fluorescence in situ hybridization.
We propose that up-regulation of ERG in human prostate cancer activates cell invasion programs that subsequently displace basal cells by neoplastic epithelium.