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Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma.

TitleAberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma.
Publication TypeJournal Article
Year of Publication2002
AuthorsSato, F., Shibata D., Harpaz N., Xu Y., Yin J., Mori Y., Wang S., Olaru A., Deacu E., Selaru F. M., Kimos M. C., Hytiroglou P., Young J., Leggett B., Gazdar A. F., Toyooka S., Abraham J. M., & Meltzer S. J.
JournalCancer Res
Date Published2002 Dec 01
KeywordsColitis, Ulcerative, Colorectal Neoplasms, Disease Progression, DNA Methylation, Humans, Membrane Proteins, Microsatellite Repeats, Neoplasm Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Tumor Cells, Cultured

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.

Alternate JournalCancer Res.
PubMed ID12460892
Grant List5U01CA8497102 / CA / NCI NIH HHS / United States
CA77057 / CA / NCI NIH HHS / United States
CA85069 / CA / NCI NIH HHS / United States
CA95323 / CA / NCI NIH HHS / United States
DK47717 / DK / NIDDK NIH HHS / United States


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