Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma.
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.
Sato
Fumiaki
F
Gastroenterology Division, Department of Medicine, University of Maryland School of Medicine and Gastroenterology Service, Baltimore, Maryland 21201, USA.
Shibata
David
D
Harpaz
Noam
N
Xu
Yan
Y
Yin
Jing
J
Mori
Yuriko
Y
Wang
Suna
S
Olaru
Andreea
A
Deacu
Elena
E
Selaru
Florin M
FM
Kimos
Martha C
MC
Hytiroglou
Prodromos
P
Young
Joanne
J
Leggett
Barbara
B
Gazdar
Adi F
AF
Toyooka
Shinichi
S
Abraham
John M
JM
Meltzer
Stephen J
SJ
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
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C423567:TMEFF2 protein, human