Previously we discovered that gene fusions between the 5'-untranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases.
We conducted a nested case-control study, including 370 cases and 2,470 controls, to evaluate associations between pre-diagnostic α- and β-carotene, α- and γ-tocopherol, β-cryptoxanthin, lutein, lycopene, retinol, and selenium with the risk of prostate cancer by ERG protein expression status (a marker of TMPRSS2:ERG).
Here, we propose to develop an assay for prostate cancer diagnosis using oligonucleotide-functionalized quantum dot and magnetic microparticle for optical detection of rearranged <i>TMPRSS2-ERG</i> fusion genes at a low concentration in urine.
Two studies found that the associations between obesity and prostate cancer (ie, fewer low-grade cancers and yet more aggressive cancers) was limited to men with TMPRSS2-ERG-positive tumors.
Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers.
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.
The TMPRSS2-ERG gene fusion resulting in ERG overexpression has been found in around 50% of prostate cancers (PCa) and is a very early event in tumorigenesis.
Importantly, androgens exert a major role in PCa formation and progression and one of the hypothesized mechanism proposed has been linked to the chromosomal rearrangement of the androgen regulated gene TMPRSS2 with ERG.
TMPRSS2:ERG is the most frequent gene rearrangement identified in prostate cancer, but whether it is involved in prostate cancer bone metastases is largely unknown.
Recently, it was shown that up to 80% of prostate tumours harbour at least one such gene fusion, and that the most common fusion event, between the prostate-specific TMPRSS2 gene and the ERG oncogene, is a critical, and probably early factor in prostate cancer development.
Moreover, TMPRSS2-ERG affects the pattern of metastatic spread by increasing the incidence of tumors in hind limbs and spine, which are two of the most frequent sites of human PCa metastases.
In two similarly treated IGRT cohorts, TMPRSS2-ERG status was not prognostic for bRFR, in disagreement with the hypothesis that these prostate cancers have DNA repair defects that render them clinically more radiosensitive.
We integrated chromatin-immunoprecipitation-coupled sequencing and microarray expression profiling in TMPRSS2-ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor-binding sites (ARBSs).
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.
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.