Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer

Schaefer, Georg; Jm, Mosquera; Ramoner, Reinhold; K, Park; Romanel, Alessandro; Steiner, Eberhard; Horninger, Wolfgang; Bektic, Jasmin; Ladurner-Rennau, Michael; Rubin, Mark A.; Demichelis, Francesca; Klocker, Helmut

doi:10.1038/pcan.2013.4

Cited by 60 publications

(51 citation statements)

References 45 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, a significant association between younger patients (aged <69 years) and a positive ERG expression status, as well as ERG intensity, was observed in our Malaysian cohort as a whole. This correlation was also observed in studies among Japanese and European CaP patients (17,43), which suggests that ERG rearrangement may be particularly important in patients with early-onset CaP.…”

Section: Discussionsupporting

confidence: 59%

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Kelly

Kong

Dobi

et al. 2014

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

show abstract

Section: Discussionsupporting

confidence: 59%

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Kelly

Kong

Dobi

et al. 2014

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…This cell line expresses a high level of wild-type androgen receptor, which mimics AR upregulation seen in the majority of androgen-refractory PCa (Edwards, et al, 2003). Furthermore, it harbors a TMPRSS2-ERG gene rearrangement found in 50%–70% of prostate tumors (Schaefer, et al, 2013). Overexpression of the encoded ERG fusion protein was reported to modulate AR signaling (Yu, et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

“…Using ChIP-seq we profiled genome wide androgen dependent AR binding sites in DUCaP cells, which harbor a TMPRSS2-ERG gene rearrangement, a genetic alteration found in 50 to 70% of prostate tumors (Rubin, et al, 2011; Schaefer, et al, 2013). A total number of 39,156 ARBSs was detected in the DUCaP cells, which is markedly higher than the number of binding sites found in the LNCaP cell line and comparable to the binding sites identified in the VCaP cells, a bone-metastasis counterpart of DUCaP derived from the same patient (Massie, et al, 2011; van Bokhoven, et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

Narisu

Schlick

et al. 2015

Human Mutation

View full text Add to dashboard Cite

Genome-wide association studies have identified genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin-IP 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). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH), was within a novel putative auxiliary AR binding motif, which is enriched in the neighborhood of canonical androgen responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of melanophilin in primary prostate tumors was significantly lower in those with the G compared to the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favourable PCa risk profile points out a tumor suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH.

show abstract

“…In some studies patient age and TMPRSS2-ERG fusion were found to be correlated. [26,27] But we didn't find any significant correlation between age and the fusion. More studies are needed to demonstrate the exact state of that relationship.…”

Section: Discussionmentioning

confidence: 83%

TMPRSS2-ERG gene fusion in Turkish patients with localized prostate cancer: results of radical prostatectomy specimens

Yılmaz

Berber

Okçelik

et al. 2016

Turkish Journal of Urology

View full text Add to dashboard Cite

Objective: Our aim was to evaluate and determine the frequency of Transmembrane protease, serine 2 (TMPRSS2)-ERG fusion in Turkish patients with clinically localized prostate cancer by using immunohistochemistry and reveal its relationship with clinicopathologic variables. Material and methods:Radical prostatectomy specimens of 99 patients, who underwent radical retropubic prostatectomy for localized cancer, between January 2002 and December 2011 were analyzed in the study. To detect ERG fusions, monoclonal ERG antibodyclone ID: EPR3864 (Epitomics, San Diego, CA, USA) and monoclonal anti-ERG antibody (9FY) (BiocareMedical, LLC, USA) were used. The immunistochemical expression of ERG protein was assessed as positive or negative regardless of stain intensity. Patients' age, total and primary Gleason scores, PSA levels, prostate volumes, tumor volumes, tumor stages and perineural invasion status were analysed retrospectively. Total fusion rate and correlation between the variables and fusion were evaluated. Results:Mean age, prostate volume, tumor volume, PSA value of 99 patients were 62.02 years (±5.93), 50.02 cc (±20.67), 3.19 cc (±4.16), and 9.34 ng/mL (±3.37) respectively. TMPRSS2-ERG fusion was seen in 46 (46.5%) of 99 patients. When the variables analysed with independent samples t test to predict fusion (+) status, none of them was found to be statistically significant. When evaluated by logistic regression analysis for (+) or (-) status, only tumor stage was found to be statistically significantly correlated with fusion (p=0.049). Conclusion:The incidence of TMPRSS-ERG fusion in patients with localised prostate cancer in our study with Turkish population was found as 46.5%. Only tumor stage correlated with TMPRSS2-ERG fusion.

show abstract

Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer

Cited by 60 publications

References 45 publications

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

TMPRSS2-ERG gene fusion in Turkish patients with localized prostate cancer: results of radical prostatectomy specimens

Contact Info

Product

Resources

About