Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions

Details

Serval ID
serval:BIB_41C5217C0119
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Monoallelic methylation of the APC promoter is altered in normal gastric mucosa associated with neoplastic lesions
Journal
Cancer Research
Author(s)
Clement  G., Bosman  F. T., Fontolliet  C., Benhattar  J.
ISSN
0008-5472 (Print)
Publication state
Published
Issued date
2004
Volume
64
Number
19
Pages
6867-6873
Notes
DA - 20041006LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov'tRN - 0 (Adenomatous Polyposis Coli Protein)SB - IM
Abstract
Adenomatous polyposis coli (APC) promoter hypermethylation has been reported frequently in normal gastric mucosa, but it remained to be clarified whether this occurs in every individual. In this study, methylation of the APC promoter was analyzed in histologically normal-appearing gastric mucosa samples by methylation-sensitive single-strand conformation analysis and by a methylation-sensitive dot blot assay. Epithelial cell samples were collected by microdissection from tissue sections. Equal amounts of methylated and unmethylated APC alleles were found in all gastric mucosa samples from patients without any gastric lesions (20 samples). Allele-specific methylation analysis showed that the methylation of the APC promoter was monoallelic; however, which allele was methylated depended on the cell type. Increased or decreased methylation was found in 10 of 36 (28%) normal gastric mucosa samples adjacent to a gastric or esophageal adenocarcinoma. No allelic loss was found at the APC locus. Modification of the methylation status was also found in 3 of 21 (14%) normal-appearing gastric mucosa samples adjacent to intestinal metaplasia. In contrast, all normal mucosa samples in cases with chronic gastritis but without metaplasia or dysplasia showed a monoallelic methylation pattern. Our results indicate the following: (a) In normal gastric mucosa, the APC promoter shows monoallelic methylation, which is not due to imprinting but most likely due to allelic exclusion; (b) the excluded allele differs between foveolar and glandular epithelial cells; (c) the APC methylation pattern is frequently altered in normal-appearing gastric mucosa of gastric or esophageal adenocarcinoma patients; and (d) such alterations also occur in normal gastric mucosa adjacent to intestinal metaplasia
Keywords
Adenocarcinoma/genetics/metabolism/Pathology/Adenomatous Polyposis Coli Protein/biosynthesis/Aged/Alleles/Barrett Esophagus/DNA Methylation/Esophageal Neoplasms/Gastric Mucosa/physiology/Genes,Apc/Humans/Intestines/Loss of Heterozygosity/Male/Metaplasia/Middle Aged/Promoter Regions (Genetics)
Pubmed
Web of science
Create date
29/01/2008 18:34
Last modification date
20/08/2019 13:42
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