%0 Journal Article
%T Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma
%A Eric Smith
%A Neville J De Young
%A Sandra J Pavey
%A Nicholas K Hayward
%A Derek J Nancarrow
%A David C Whiteman
%A B Mark Smithers
%A Andrew R Ruszkiewicz
%A Andrew D Clouston
%A David C Gotley
%A Peter G Devitt
%A Glyn G Jamieson
%A Paul A Drew
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-75
%X We examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC.We found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.The incidence of esophageal adenocarcinoma (EAC) is increasing rapidly and patient outcomes remain poor. Known risk factors for EAC include obesity, gastro-esophageal reflux, and the presence of Barrett's esophagus (BE). Repeated injury from gastro-duodenal reflux is thought to result in the replacement of the esophageal squamous mucosa with a metaplastic columnar
%U http://www.molecular-cancer.com/content/7/1/75