title: Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma.
abstract: The HPP1 gene was cloned as a frequently methylated gene in hyperplastic polyps of the colon. It has been shown that HPP1 expression is silenced by HPP1 gene hypermethylation in sporadic colorectal cancers. To determine the role of HPP1 in ulcerative colitis (UC)-associated carcinogenesis, the prevalence of HPP1 methylation was investigated in three different histological stages of UC-associated carcinogenesis (non-neoplastic UC colon, dysplasia, and carcinoma). Quantitative methylation-specific PCR and quantitative reverse transcription-PCR were used to determine HPP1 gene methylation and expression levels, respectively. HPP1 methylation was observed in 24 of 48 (50%) adenocarcinomas and in 4 of 10 (40%) dysplasias. In contrast, no non-neoplastic UC mucosa showed HPP1 methylation. HPP1 expression in the HCT116 colon cancer cell line was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine. In conclusion, our data suggest that methylation of HPP1 is a relatively common early event in UC-associated carcinogenesis. HPP1 offers potential as a biomarker for the early detection of cancer or dysplasia in UC.
authors.affiliation: Gastroenterology Division, Department of Medicine, University of Maryland School of Medicine and Gastroenterology Service, Baltimore, Maryland 21201, USA.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.forename: Noam
authors.initials: N
authors.lastname: Harpaz
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Andreea
authors.initials: A
authors.lastname: Olaru
authors.forename: Elena
authors.initials: E
authors.lastname: Deacu
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
authors.forename: Martha C
authors.initials: MC
authors.lastname: Kimos
authors.forename: Prodromos
authors.initials: P
authors.lastname: Hytiroglou
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Barbara
authors.initials: B
authors.lastname: Leggett
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D018450:Disease Progression; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C423567:TMEFF2 protein, human