1062 EPIGENETIC CHANGES IN BLADDER TUMORS OF YOUNG PATIENTS

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20121062 EPIGENETIC CHANGES IN BLADDER TUMORS OF YOUNG PATIENTS Willemien Beukers, Aleksander Hercegovac, Marcel Vermeij, Charlotte Blok, Madelon van der Aa, Ellen Zwarthoff, and Tahlita Zuiverloon Willemien BeukersWillemien Beukers Rotterdam, Netherlands More articles by this author , Aleksander HercegovacAleksander Hercegovac Rotterdam, Netherlands More articles by this author , Marcel VermeijMarcel Vermeij Rotterdam, Netherlands More articles by this author , Charlotte BlokCharlotte Blok Leiden, Netherlands More articles by this author , Madelon van der AaMadelon van der Aa Leiden, Netherlands More articles by this author , Ellen ZwarthoffEllen Zwarthoff Rotterdam, Netherlands More articles by this author , and Tahlita ZuiverloonTahlita Zuiverloon Rotterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1168AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer is a disease of the elderly and is rare under the age of 40, with an incidence of only 0.03% below the age of 20. Previous studiesshowed that tumors in young patients lack or have a much lower incidence of (epi)genetic aberrations typical for bladder cancer. This raises the question what drives tumorigenesis in young patients.Polycomb group (PcG) protein complexes play an important role in lineage choices during embryogenesis. Aberrant methylation of PcG target genes is thought to be an early event in the formation of many carcinomas. We hypothesized that hypermethylation of genes that are targets of PcG complexes could play a role in bladder cancer development in young patients. METHODS Bladder tumors from 167 patients were included. Patients were stratified by age at diagnosis into four groups: under the age of 20, 20-40 years, 40-60 years and above 60 years. We studied 5 genes that were identified in an earlier study as being methylated in bladder tumors and that were also targets of PcG complexes (Kandimalla et al., submitted). Methylation analysis was performed using Bisulfite Specific PCR and Single Nucleotide Primer Extension. Methylation ratios were calculated by using the unmethylated and methylated signal, which resulted in a methylation percentage. The outcome represented the amount of methylated cells within one tumor. Genes with similar methylation ratios in all four age groups were considered as potential cancer initiating candidates. RESULTS Four genes showed higher methylation ratios in tumors from older patients: ONECUT2 (p<0.001), MEIS1 (p=0.019), SOX21 (p<0.001) and OTX1 (p<0.001). Only PCDH7 exhibited similar mean methylation percentages in all four age groups, i.e. <20yr 54%; 20-40yr 59%; 40-60yr 59%; >60yr 67%. CONCLUSIONS Patients under the age of 20 are a biologically and molecularly distinct group. Tumors from young patients showed substantially less methylation for most markers compared to tumors from patients in the older age groups. Only PCDH7 showed high methylation ratios in all four age groups and could therefore play an important factor in early urothelial carcinogenesis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e430-e431 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Willemien Beukers Rotterdam, Netherlands More articles by this author Aleksander Hercegovac Rotterdam, Netherlands More articles by this author Marcel Vermeij Rotterdam, Netherlands More articles by this author Charlotte Blok Leiden, Netherlands More articles by this author Madelon van der Aa Leiden, Netherlands More articles by this author Ellen Zwarthoff Rotterdam, Netherlands More articles by this author Tahlita Zuiverloon Rotterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...