One patient with aggressive prostate cancer carried a deletion and a stop codon in exon 11, leading to inactivation of the serine protease domain in TMPRSS2.
Gene fusion between TMPRSS2 promoter and the ERG proto-oncogene is a major genomic alteration found in over half of prostate cancers (CaP), which leads to aberrant androgen dependent ERG expression.
High-level EZH2 staining was also associated with TMPRSS2:ERG rearrangement and ERG expression in prostate cancers (P < 0.0001) and was linked to deletions of PTEN, 6q15, 5q21 and 3p13 (P < 0.0001 each) particularly in ERG-negative cancers.
Collectively, our findings established that Ets2 is a tumor suppressor gene in prostate cancer, and its loss along with other genes within the TMPRSS2-ERG interstitial region contributes to disease progression.
The transmembrane serine protease 2 (TMPRSS2) gene encodes a type II transmembrane protein which, due to its cell surface localization, could be a potentially useful predictive marker for PCa.
Fifty of 150 (33%) of the prostatectomy specimens and 28 of 76 (37%) of the hormone-refractory prostate cancers on the tissue microarrays carried the TMPRSS2:ERG rearrangement.
This study aims to investigate prevalence of ETS-related gene (ERG) oncoprotein overexpression in Filipinos as surrogate of TMPRSS2-ERG gene fusions, using a highly specific monoclonal antibody (ERG-MAb), and conduct the first attempt to study the role of genetic alterations in the aggressive tumor biologic behaviour of CaP among Filipinos.
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.
These findings suggest that TMPRSS2-ERG with Edel is an aggressive and, in this study, uniformly lethal molecular subtype of prostate cancer associated with androgen-independent disease.
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.
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.
In conclusion, our study identifies an association of NBS1 expression with surrogates of genomic instability in prostate cancer including TMPRSS2-ERG rearrangements and PTEN deletion.
Therapeutic delivery of miR-200c may provide personalized treatment for patients with the molecular subtype of PCa that harbors TMPRSS2-ERG gene fusions.
Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusions are the most common genetic aberration so far described in human malignancies.
SLC45A3-ERG and TMPRSS2-ERG rearrangements and their association with ERG and PTEN expression and with clinical and pathological features have been analyzed in 80 PrCa (PSMAR-Biobank, Barcelona, Spain).