TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer

Steurer, Stefan; Mayer, Pascale Sophia; Adam, Meike; Krohn, Antje; Koop, Christina; Ospina-Klinck, Daniel; Tehrani, Ali Attarchi; Simon, Ronald; Tennstedt, Pierre; Graefen, Markus; Wittmer, Corinna; Brors, Benedikt; Plass, Christoph; Korbel, Jan O.; Weischenfeldt, Joachim; Sauter, Guido; Huland, Hartwig; Tsourlakis, Maria Christina; Minner, Sarah; Schlomm, Thorsten

doi:10.1016/j.eururo.2014.06.027

Cited by 57 publications

(62 citation statements)

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Section: Tmprss2:erg Fusionmentioning

confidence: 99%

“…ETS fusion-type cancers are believed to represent a genetically distinct subset of PCa characterized by deletions of the phosphatase and tensin homolog (PTEN) gene and of chromosome 3p, whereas deletions of 5q and 6q prevail in fusion-negative cancers [14][15][16][17]. Although gene fusions in general, and specifically ETS fusions, have been associated with the early onset of PCa [18,19], the clinical utility of the gene fusion as a prognostic or predictive tool is still unclear.…”

Section: Tmprss2:erg Fusionmentioning

confidence: 99%

“…Ten studies reported the prognostic value of the gene fusion in radical prostatectomy (RP) cohorts [19][20][21][22][23][24][25][26][27][28]. In 6 of the 10 studies, TMPRSS2:ERG fusion status was not associated with outcome after surgery [19,21,22,24,27,29]. In one Urine-detected rearrangement associated with positive repeat biopsy aCGH = array comparative genomic hybridization; ADT = androgen-deprivation therapy; AS = active surveillance; BCR = biochemical recurrence; CRPC = castration-resistant prostate cancer; DSS = disease-specific survival; FISH = fluorescence in situ hybridization; HR = hazard ratio; IHC = immunohistochemistry; IMRT = intensity-modulated radiation therapy; NA = not applicable; NR = not reported; OS = overall survival; PCa = prostate cancer; PSA = prostate-specific antigen; RT-PCR = reverse transcriptase polymerase chain reaction; RP = radical prostatectomy; SNP = single nucleotide polymorphism; TURP = transurethral resection of prostate; WW = watchful waiting.…”

Section: Tmprss2:erg Fusionmentioning

confidence: 99%

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Genomic Predictors of Outcome in Prostate Cancer

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Section: Tmprss2:erg Fusionmentioning

confidence: 99%

Section: Tmprss2:erg Fusionmentioning

confidence: 99%

Section: Tmprss2:erg Fusionmentioning

confidence: 99%

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Genomic Predictors of Outcome in Prostate Cancer

et al. 2015

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“…Некоторые функ-циональные исследования показали, что гиперэкс-прессия ERG как единственное изменение в клетке, несмотря на очевидную роль в онкогенезе, не являет-ся достаточной для развития опухоли, что рождает предположения о необходимости дополнительных, дальнейших изменений [34][35][36]. Попытки связать сли-яние T2: ERG с агрессивностью рака и клиническим исходом на сегодняшний день также не увенчались успехом [37][38][39][40], особенно при использовании после радикального лечения [см. 29].…”

Section: о н к о у р о л о г и я 100unclassified

Clinical relevance of prostate cancer genetic characterization: literature review

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Носов³

et al. 2015

Onkourologiya

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“…As many as 50% of CaP patients possess a fusion between the androgen-regulated gene, TMPRSS2, and the ETS family member, TMPRSS2:ERG 342 .While a correlation between ERG expression and clinical and pathological parameters has not been observed, specificity and recurrence of ERG in CaP suggests that it may be a useful adjunct diagnostic biomarker 343 . In another study a strong link was recorded between ERG activation, young patient age and low grade cancer 344 .…”

Section: Discussionmentioning

confidence: 99%

Multiple markers for the non-invasive diagnosis and characterisation of prostate cancer

Roberts¹

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The early detection of prostate cancer (CaP), the most common internal cancer in men, is limited by an absence of biomarkers that accurately reflect clinically significant disease.Currently, the prostate cancer antigen 3 (PCA3) test in combination with TMPRSS2-ERG fusion gene detection in urine obtained following rectal prostatic massage represent arguably the best standalone biomarkers for CaP but are not widely used in comparison with serum prostate specific antigen (PSA). Limitations in CaP diagnosis and characterisation may be overcome by use of naturally-produced, prostate-specific biofluids, such as ejaculate and post-ejaculate urethral washings (PEUW). Ejaculate is known to contain prostatic cells and relevant molecules in the non-cellular component, while PEUW may contain these as well as biomarkers reflective of systemic changes due to or causing CaP.The overall aim of this thesis was to use molecular and metabolomic nuclear magnetic resonance (NMR)-based detection methods to study prostatic fluid derived from ejaculate and PEUW to improve CaP diagnosis. Specifically, this thesis sought to optimise ejaculate sample processing for metabolomics studies and evaluate the diagnostic performance of mRNA, microRNA and metabolomic markers in ejaculate to complement serum PSA in detecting clinically significant CaP. Furthermore, this thesis investigated the feasibility and performance of PEUW-based mRNA and metabolomic biomarker performance attributable to the presence of ejaculate in urine to reflect local prostatic and systemic alterations in order to more accurately detect clinically significant CaP. Dependent clinical variables considered were absolute (positive/negative) and clinically significant (present/absent) CaP as well as risk groups (low, intermediate, high) according to the D'Amico criteria.Using a NMR-based metabolomics enzyme kinetics study design, the addition of tartrate and cooling of ejaculate samples improved the stability of choline and phosphorylcholine concentrations. Sample collection into a sterile urine jar containing 5 mM (on-site) or 10 mM (off-site) tartrate in 20 ml PBS solution cooled to 277 K and cooled during transport until processing would result in at most a 2-3% change in choline and phosphorylcholine to facilitate sample collection off-site without significant effect on choline-based metabolites.Following prostatic cell RNA isolation, amplification and qPCR for β2-microglobulin (β2M), PSA, PCA3 and Hepsin in ejaculate, adequate RNA for all assays was obtained for 66 patients and determined that a Hepsin:PCA3 ratio in ejaculate together with serum PSA best predicted absolute CaP (AUC= 0.724 vs 0.676) and csCaP (AUC= 0.701 vs 0.680).iii Matched mRNA and microRNA expression was possible for a subgroup of patients (n=20) Lipids/lipoproteins dominated spectra of high grade samples. Overall CaP prediction using metabolites described in previous studies was not validated. However, findings suggest that incorporation of in vitro NMR-based metabolomics may translate to in v...

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TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer

Cited by 57 publications

References 9 publications

Genomic Predictors of Outcome in Prostate Cancer

Genomic Predictors of Outcome in Prostate Cancer

Clinical relevance of prostate cancer genetic characterization: literature review

Multiple markers for the non-invasive diagnosis and characterisation of prostate cancer

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