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

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

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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

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wong, D. J., Barrett, M. T., 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.