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• W2155488525 abstract "No AccessJournal of UrologyInvestigative Urology1 Jul 2013Hypermethylation of the Polycomb Group Target Gene PCDH7 in Bladder Tumors from Patients of All Ages Willemien Beukers, Aleksander Hercegovac, Marcel Vermeij, Raju Kandimalla, Arina C. Blok, Madelon M.N. van der Aa, Ellen C. Zwarthoff, and Tahlita C.M. Zuiverloon Willemien BeukersWillemien Beukers Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author , Aleksander HercegovacAleksander Hercegovac Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author , Marcel VermeijMarcel Vermeij Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author , Raju KandimallaRaju Kandimalla Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author , Arina C. BlokArina C. Blok Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands More articles by this author , Madelon M.N. van der AaMadelon M.N. van der Aa Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands More articles by this author , Ellen C. ZwarthoffEllen C. Zwarthoff Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author , and Tahlita C.M. ZuiverloonTahlita C.M. Zuiverloon Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.01.078AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Bladder tumors in patients younger than 20 years show a low incidence of the genetic and epigenetic aberrations typically found in older patients. One of the most common epigenetic aberrations in human malignancies is DNA hypermethylation. Polycomb group complexes have an important role during lineage choices in embryogenesis and their target genes are 12 times more likely to be methylated than nonpolycomb group target genes. We hypothesized that methylation of polycomb group target genes is an early event in urothelial carcinogenesis and thus might be observed in young patients. Materials and Methods: We stratified 167 patients by age into 4 groups, including age less than 20 years in 14, 20 to 40 in 48, 40 to 60 in 47 and greater than 60 in 58. Five previously identified polycomb group target genes (MEIS1, ONECUT2, OTX1, PCDH7 and SOX21) were selected for methylation analysis. Methylation ratios were calculated by using the unmethylated and methylated signal. The outcome represented the fraction of methylated cells within one tumor. Genes with similar methylation ratios in all age groups were considered as potential bladder cancer initiating candidates. Results: Three genes showed higher methylation ratios in tumors from older patients, including ONECUT2, SOX21 and OTX1 (each p <0.001). MEIS1 showed a similar methylation ratio in all groups but the median methylation ratio was low. PCDH7 showed a similar median methylation percent in all age categories, ie 54% at less than 20, 59% at 20 to 40, 59% at 40 to 60 and 67% at greater than 60 years (p = 0.1). Conclusions: Tumors from young patients showed less methylation for most markers. PCDH7 showed high methylation ratios in all age categories. Therefore, it could have an important role in early urothelial carcinogenesis. References 1 : Bladder carcinoma in patients less than 40 years of age. Urol Int1989; 44: 81. Google Scholar 2 : Transitional cell carcinoma of the bladder in young adults. Br J Urol1993; 72: 749. 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Google Scholar 17 : Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. Adv Anat Pathol2011; 18: 79. Google Scholar 18 : A methylation assay for the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences in voided urine. BJU Int2012; 109: 941. Google Scholar 19 : Clustered protocadherin family. Dev Growth Differ2008; 50: S131. Google Scholar 20 : Cloning, expression analysis, and chromosomal localization of BH-protocadherin (PCDH7), a novel member of the cadherin superfamily. Genomics1998; 49: 458. Google Scholar 21 : Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol2006; 24: 778. Google Scholar 22 : Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res2004; 64: 4040. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: Aberrant Methylated Key Genes of Methyl Group Metabolism within the Molecular Etiology of Urothelial CarcinogenesisJournal of Urology, VOL. 200, NO. 5, (947-948), Online publication date: 1-Nov-2018.Andersson K (2018) This Month in Investigative UrologyJournal of Urology, VOL. 190, NO. 1, (6-7), Online publication date: 1-Jul-2013. Volume 190Issue 1July 2013Page: 311-316 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordspolycomb-group proteinsurinary bladderurinary bladder neoplasmsmethylationadolescentAcknowledgmentsThe PALGA-foundation assisted with patient selection and facilitating tissue collection from hospitals.MetricsAuthor Information Willemien Beukers Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Aleksander Hercegovac Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Marcel Vermeij Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Raju Kandimalla Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Arina C. Blok Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands More articles by this author Madelon M.N. van der Aa Department of Urology, Leiden University Medical Centre, Leiden, The Netherlands More articles by this author Ellen C. Zwarthoff Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Tahlita C.M. Zuiverloon Department of Pathology, Erasmus MC, Rotterdam, The Netherlands More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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