title: Epigenetic alterations of adenomatous polyposis coli (APC), retinoic acid receptor beta (RARβ) and survivin genes in tumor tissues and voided urine of bladder cancer patients.
abstract: The CpG promoter methylation has been reported to occur frequently in bladder cancer. Moreover, analysis of gene methylation has been shown to be feasible from voided urine and can be detected with a high degree of sensitivity. The aim of this present study is to determine how methylation patterns of APC, RAR&#946; and Survivin genes change during bladder carcinogenesis and to evaluate whether DNA methylation could be detected in urine sediment. Using the sensitive assay of MSP, we explored the promoter methylation status for the three genes in tumor specimens and urine sediment DNA from 32 bladder cancer patients. Methylation frequencies of the tested genes in tumor specimens were 100%, 75% and 84.4% for APC, RAR&#946; and Survivin, respectively. Hypermethylation of APC was found in all pathological grades and stages of bladder cancer. More frequent promoter hypermethylation of RAR&#946; and Survivin was observed in high grade tumors and the hypermethylation increased from low to high stages, but there was no significant correlation between stages/grades and hypermethylation of these two gene promoters. In order to investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status in urine samples of bladder cancer patients. Methylation of the tested genes in urine sediment DNA was detected in the majority of cases that were hypermethylated in tumor samples (93.7%) and the frequencies were 79.3% 70.8% and 96.3% for APC, RAR&#946; and Survivin, respectively. Our results indicate that methylation of APC, RAR&#946; and Survivin gene promoters is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancer.
authors.affiliation: Unité de Biologie et recherché Médicale, Centre National de l’Energie, des Sciences et Techniques Nucléaires, Rabat, Maroc.
authors.forename: N
authors.initials: N
authors.lastname: Berrada
authors.forename: S
authors.initials: S
authors.lastname: Amzazi
authors.forename: R
authors.initials: R
authors.lastname: Ameziane El Hassani
authors.forename: L
authors.initials: L
authors.lastname: Benbacer
authors.forename: M
authors.initials: M
authors.lastname: El Mzibri
authors.forename: M
authors.initials: M
authors.lastname: Khyatti
authors.forename: J
authors.initials: J
authors.lastname: Chafiki
authors.forename: M
authors.initials: M
authors.lastname: Abbar
authors.forename: A
authors.initials: A
authors.lastname: Al Bouzidi
authors.forename: A
authors.initials: A
authors.lastname: Ameur
authors.forename: M
authors.initials: M
authors.lastname: Attaleb
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D018168:Receptors, Retinoic Acid; D000077022:Survivin; C082925:retinoic acid receptor beta