p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus

Détails

ID Serval
serval:BIB_28E8488DAEA3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus
Périodique
Gastroenterology
Auteur(s)
Bian  Y. S., Osterheld  M. C., Fontolliet  C., Bosman  F. T., Benhattar  J.
ISSN
0016-5085 (Print)
Statut éditorial
Publié
Date de publication
2002
Volume
122
Numéro
4
Pages
1113-1121
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Résumé
BACKGROUND & AIMS: The potential role of p16 inactivation by CDKN2A/p16 promoter hypermethylation and/or loss of heterozygosity (LOH) of the CDKN2A gene was investigated in neoplastic progression of Barrett's esophagus. METHODS: CDKN2A promoter hypermethylation was studied by methylation sensitive single-strand conformation analysis and sequencing using bisulfite modified DNA in Barrett's esophageal adenocarcinomas, premalignant lesions, and normal squamous esophageal epithelium. All of the lesions of interest were sampled by microdissection from paraffin-embedded fixed tissue sections. RESULTS: No methylation of the CDKN2A promoter was found in normal esophageal squamous cell epithelia, whereas methylation was detected in 18 of 22 (82%) adenocarcinomas and 10 of 33 (30%) premalignant lesions, including 4 of 12 (33%) samples with intestinal metaplasia only. LOH at the CDKN2A gene locus was found in 68% of adenocarcinomas and in 55% of premalignant lesions. Of 28 samples without p16 immunoreactivity, 25 (89%) showed CDKN2A promoter hypermethylation with or without LOH of CDKN2A. Only 2 (8%) samples expressing p16 protein were found to be methylated; these showed a mixture of completely methylated and unmethylated CDKN2A promoters. In 7 of 19 (37%) informative samples without LOH of CDKN2A, the CDKN2A promoter was found to be methylated at both alleles. Loss of p16 protein expression was strongly associated with CDKN2A promoter hypermethylation (P < 0.00001), but not with LOH (P = 0.33). CONCLUSIONS: Our results indicate that methylation of the CDKN2A promoter is the predominant mechanism for p16 inactivation. This hypermethylation is a very common event in esophageal adenocarcinoma and occurs as early as metaplasia
Mots-clé
Adenocarcinoma/genetics/physiopathology/Barrett Esophagus/Cyclin-Dependent Kinase Inhibitor p16/metabolism/DNA Methylation/Disease Progression/Esophageal Neoplasms/Gene Expression Regulation,Neoplastic/Humans/Loss of Heterozygosity/Precancerous Conditions/Promoter Regions (Genetics)/physiology/Tumor Cells,Cultured
Pubmed
Web of science
Création de la notice
29/01/2008 19:36
Dernière modification de la notice
20/08/2019 14:08
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