Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis

Fumiaki Sato, Yan Xu, Jing Yin, Yuriko Mori, Tong Tong Zou, Suna Wang, Kena Desai, Florin M. Selaru, John M. Abraham, Stephen J. Meltzer, Fumiaki Sato, Yan Xu, Jing Yin, Yuriko Mori, Tong Tong Zou, Suna Wang, Kena Desai, Florin M. Selaru, John M. Abraham, Stephen J. Meltzer & 3 others Noam Harpaz, Anatoly Leytin, David Shibata

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Abstract

The p14ARF protein directly inhibits the MDM-2 oncoprotein, which mediates degradation of the p53 protein. It has been shown that p14ARF expression is frequently down-regulated by p14ARF gene hypermethylation in colorectal cancer. To determine whether p14ARF inactivation was involved in ulcerative colitis (UC)-associated carcinogenesis, the frequency and timing of p14ARF methylation was investigated in four different histological stages of UC-associated carcinogenesis. Methylation-specific PCR and bisulfite sequencing were used to determine the prevalence of p14ARF gene methylation. p14ARF methylation was observed in 19 of 38 (50%) adenocarcinomas, 4 of 12 (33%) dysplasias, and 3 of the 5 (60%) nonneoplastic UC mucosae. In contrast, 3 of 40 (3.7%) normal tissues showed p14ARF methylation (X2 test: P = 0.0003). Bisulfite sequencing was used to analyze 28 CpGs of p14ARF gene in 20 samples. The number of methylated CpGs ranged from 0 to 4, 0 to 20, and 0 to 28 in the normal, dysplastic, and carcinomatous samples, respectively (Kruskall-Wallis test: P = 0.0005). Densely methylated alleles were detected only in carcinomas by bisulfite sequencing. In conclusion, our data suggest that methylation of p14ARF is a relatively common early event in UC-associated carcinogenesis. p14ARF offers potential as a biomarker for the early detection of cancer or dysplasia in UC. Finally, analyses of p14ARF methylation in other organs should explore not only frank cancers but other premalignant lesions.

Original languageEnglish (US)
Pages (from-to)1148-1151
Number of pages4
JournalCancer Research
Volume62
Issue number4
StatePublished - Feb 15 2002

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Tumor Suppressor Protein p14ARF
Ulcerative Colitis
Carcinogenesis
Methylation
Genes
Oncogene Proteins
Early Detection of Cancer
Proteolysis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sato, F., Xu, Y., Yin, J., Mori, Y., Zou, T. T., Wang, S., ... Shibata, D. (2002). Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis. Cancer Research, 62(4), 1148-1151.

Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis. / Sato, Fumiaki; Xu, Yan; Yin, Jing; Mori, Yuriko; Zou, Tong Tong; Wang, Suna; Desai, Kena; Selaru, Florin M.; Abraham, John M.; Meltzer, Stephen J.; Sato, Fumiaki; Xu, Yan; Yin, Jing; Mori, Yuriko; Zou, Tong Tong; Wang, Suna; Desai, Kena; Selaru, Florin M.; Abraham, John M.; Meltzer, Stephen J.; Harpaz, Noam; Leytin, Anatoly; Shibata, David.

In: Cancer Research, Vol. 62, No. 4, 15.02.2002, p. 1148-1151.

Research output: Contribution to journalArticle

Sato, F, Xu, Y, Yin, J, Mori, Y, Zou, TT, Wang, S, Desai, K, Selaru, FM, Abraham, JM, Meltzer, SJ, Sato, F, Xu, Y, Yin, J, Mori, Y, Zou, TT, Wang, S, Desai, K, Selaru, FM, Abraham, JM, Meltzer, SJ, Harpaz, N, Leytin, A & Shibata, D 2002, 'Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis', Cancer Research, vol. 62, no. 4, pp. 1148-1151.
Sato F, Xu Y, Yin J, Mori Y, Zou TT, Wang S et al. Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis. Cancer Research. 2002 Feb 15;62(4):1148-1151.
Sato, Fumiaki ; Xu, Yan ; Yin, Jing ; Mori, Yuriko ; Zou, Tong Tong ; Wang, Suna ; Desai, Kena ; Selaru, Florin M. ; Abraham, John M. ; Meltzer, Stephen J. ; Sato, Fumiaki ; Xu, Yan ; Yin, Jing ; Mori, Yuriko ; Zou, Tong Tong ; Wang, Suna ; Desai, Kena ; Selaru, Florin M. ; Abraham, John M. ; Meltzer, Stephen J. ; Harpaz, Noam ; Leytin, Anatoly ; Shibata, David. / Hypermethylation of the p14ARF gene in ulcerative colitis-associated colorectal carcinogenesis. In: Cancer Research. 2002 ; Vol. 62, No. 4. pp. 1148-1151.
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abstract = "The p14ARF protein directly inhibits the MDM-2 oncoprotein, which mediates degradation of the p53 protein. It has been shown that p14ARF expression is frequently down-regulated by p14ARF gene hypermethylation in colorectal cancer. To determine whether p14ARF inactivation was involved in ulcerative colitis (UC)-associated carcinogenesis, the frequency and timing of p14ARF methylation was investigated in four different histological stages of UC-associated carcinogenesis. Methylation-specific PCR and bisulfite sequencing were used to determine the prevalence of p14ARF gene methylation. p14ARF methylation was observed in 19 of 38 (50{\%}) adenocarcinomas, 4 of 12 (33{\%}) dysplasias, and 3 of the 5 (60{\%}) nonneoplastic UC mucosae. In contrast, 3 of 40 (3.7{\%}) normal tissues showed p14ARF methylation (X2 test: P = 0.0003). Bisulfite sequencing was used to analyze 28 CpGs of p14ARF gene in 20 samples. The number of methylated CpGs ranged from 0 to 4, 0 to 20, and 0 to 28 in the normal, dysplastic, and carcinomatous samples, respectively (Kruskall-Wallis test: P = 0.0005). Densely methylated alleles were detected only in carcinomas by bisulfite sequencing. In conclusion, our data suggest that methylation of p14ARF is a relatively common early event in UC-associated carcinogenesis. p14ARF offers potential as a biomarker for the early detection of cancer or dysplasia in UC. Finally, analyses of p14ARF methylation in other organs should explore not only frank cancers but other premalignant lesions.",
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AU - Wang, Suna

AU - Desai, Kena

AU - Selaru, Florin M.

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AU - Meltzer, Stephen J.

AU - Sato, Fumiaki

AU - Xu, Yan

AU - Yin, Jing

AU - Mori, Yuriko

AU - Zou, Tong Tong

AU - Wang, Suna

AU - Desai, Kena

AU - Selaru, Florin M.

AU - Abraham, John M.

AU - Meltzer, Stephen J.

AU - Harpaz, Noam

AU - Leytin, Anatoly

AU - Shibata, David

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