Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis.

ABSTRACT: Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine clu

SUBMITTER: Alvarez H 

PROVIDER: S-EPMC3069107 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature