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

Fumiaki Sato, David Shibata, 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, Stephen J. Meltzer

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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.

Original languageEnglish (US)
Pages (from-to)6820-6822
Number of pages3
JournalCancer Research
Volume62
Issue number23
StatePublished - Dec 1 2002

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Ulcerative Colitis
Methylation
Colorectal Neoplasms
Genes
Carcinogenesis
decitabine
Colon
Polymerase Chain Reaction
Polyps
Early Detection of Cancer
Colonic Neoplasms
Reverse Transcription
Mucous Membrane
Adenocarcinoma
Biomarkers
Carcinoma
Gene Expression
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sato, F., Shibata, D., Harpaz, N., Xu, Y., Yin, J., Mori, Y., ... Meltzer, S. J. (2002). Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma. Cancer Research, 62(23), 6820-6822.

Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma. / Sato, Fumiaki; Shibata, David; Harpaz, Noam; Xu, Yan; Yin, Jing; Mori, Yuriko; Wang, Suna; Olaru, Andreea; Deacu, Elena; Selaru, Florin M.; Kimos, Martha C.; Hytiroglou, Prodromos; Young, Joanne; Leggett, Barbara; Gazdar, Adi F.; Toyooka, Shinichi; Abraham, John M.; Meltzer, Stephen J.

In: Cancer Research, Vol. 62, No. 23, 01.12.2002, p. 6820-6822.

Research output: Contribution to journalArticle

Sato, F, Shibata, D, Harpaz, N, Xu, Y, Yin, J, Mori, Y, Wang, S, Olaru, A, Deacu, E, Selaru, FM, Kimos, MC, Hytiroglou, P, Young, J, Leggett, B, Gazdar, AF, Toyooka, S, Abraham, JM & Meltzer, SJ 2002, 'Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma', Cancer Research, vol. 62, no. 23, pp. 6820-6822.
Sato, Fumiaki ; Shibata, David ; Harpaz, Noam ; Xu, Yan ; Yin, Jing ; Mori, Yuriko ; Wang, Suna ; Olaru, Andreea ; Deacu, Elena ; Selaru, Florin M. ; Kimos, Martha C. ; Hytiroglou, Prodromos ; Young, Joanne ; Leggett, Barbara ; Gazdar, Adi F. ; Toyooka, Shinichi ; Abraham, John M. ; Meltzer, Stephen J. / Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma. In: Cancer Research. 2002 ; Vol. 62, No. 23. pp. 6820-6822.
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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.",
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AU - Olaru, Andreea

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AU - Selaru, Florin M.

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AU - Young, Joanne

AU - Leggett, Barbara

AU - Gazdar, Adi F.

AU - Toyooka, Shinichi

AU - Abraham, John M.

AU - Meltzer, Stephen J.

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N2 - 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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