p16(INK4a) promoter is hypermethylated at a high frequency in esophageal adenocarcinomas

David J. Wong, Michael Barrett, Reinhard Stöger, Mary J. Emond, Brian J. Reid

Research output: Contribution to journalArticle

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Abstract

Loss of heterozygosity (LOH) of 9p21, which contains the p16(INK4a) tumor suppressor gene locus, is one of the most frequent genetic abnormalities in human neoplasia, including esophageal adenocarcinomas. Only a minority of Barrett's adenocarcinomas with 9p21 LOH have a somatic mutation in the remaining p16 allele, and none have been found to have homozygous deletions. To determine whether p16 promoter hyper-methylation may be an alternative mechanism for p16 inactivation in esophageal adenocarcinomas, we examined the methylation status of the p16 promoter in flow-sorted aneuploid cell populations from 21 patients with premalignant Barrett's epithelium or esophageal adenocarcinoma. Using bisulfite modification, primer-extension preamplification, and methylation-specific PCR, we demonstrate that the methylation assay can be performed on 2 ng of DNA (~275 cells). Eight of 21 patients (38%) had p16 promoter hypermethylation and 9p21 LOH, including 3 patients who had only premalignant Barrett's epithelium. Our data suggest that promoter hypermethylation with LOH is a common mechanism for inactivation of p16 in the pathogenesis of esophageal adenocarcinomas.

Original languageEnglish (US)
Pages (from-to)2619-2622
Number of pages4
JournalCancer Research
Volume57
Issue number13
StatePublished - Jul 1 1997
Externally publishedYes

Fingerprint

Loss of Heterozygosity
Adenocarcinoma
Methylation
Barrett Esophagus
Aneuploidy
Tumor Suppressor Genes
Alleles
Polymerase Chain Reaction
Mutation
DNA
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wong, D. J., Barrett, M., Stöger, R., Emond, M. J., & Reid, B. J. (1997). p16(INK4a) promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. Cancer Research, 57(13), 2619-2622.

p16(INK4a) promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. / Wong, David J.; Barrett, Michael; Stöger, Reinhard; Emond, Mary J.; Reid, Brian J.

In: Cancer Research, Vol. 57, No. 13, 01.07.1997, p. 2619-2622.

Research output: Contribution to journalArticle

Wong, DJ, Barrett, M, Stöger, R, Emond, MJ & Reid, BJ 1997, 'p16(INK4a) promoter is hypermethylated at a high frequency in esophageal adenocarcinomas', Cancer Research, vol. 57, no. 13, pp. 2619-2622.
Wong, David J. ; Barrett, Michael ; Stöger, Reinhard ; Emond, Mary J. ; Reid, Brian J. / p16(INK4a) promoter is hypermethylated at a high frequency in esophageal adenocarcinomas. In: Cancer Research. 1997 ; Vol. 57, No. 13. pp. 2619-2622.
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