Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention Susan G. Komen for the Cure-AACR Outstanding Investigator Award for Breast Cancer Research
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[Cancer Research 62, 6820-6822, December 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Aberrant Methylation of the HPP1 Gene in Ulcerative Colitis-associated Colorectal Carcinoma1

Fumiaki Sato2, David Shibata2, Noam Harpaz, Yan Xu, Jing Yin, Yuriko Mori, Suna Wang, Andreea Olaru, Elena Deacu, Florin M. Selaru, Martha C. Kimos, Prodromos Hytiroglou, Joanne Young, Barbara Leggett, Adi F. Gazdar, Shinichi Toyooka, John M. Abraham and Stephen J. Meltzer3

Gastroenterology Division, Department of Medicine, University of Maryland School of Medicine and Gastroenterology Service, Department of Medicine, Baltimore VA Hospital, Baltimore, Maryland 21201 [F. S., Y. X., J. Yi., Y. M., S. W., A. O., E. D., F. M. S., M. C. K., J. M. A., S. J. M.]; Division of Surgical Oncology, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201 [D. S.]; Department of Pathology, The Mount Sinai School of Medicine, New York, New York 10029 [N. H., P. H.]; Gastroenterology Unit, Queensland Institute of Medical Research, Brisbane 4029, Australia [J. Yo., B. L.]; and University of Texas Southwestern Medical Center, Hamon Cancer Center, Dallas, Texas 75390 [A. F. G., S. T.]

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.




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