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

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


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
Issue number13
StatePublished - Jul 1 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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