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Int J Clin Exp Pathol 2012;5(5):382-396

Review Article
Role of epigenetic alterations in the pathogenesis of Barrett’s esophagus and
esophageal adenocarcinoma

Archana Agarwal, Rahul Polineni, Zulfiqar Hussein, Ivette Vigoda, Tushar Bhagat, Sanchari Bhattacharya, Anirban Maitra, Amit Verma

Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA 02124; Albert Einstein College of Medicine, Bronx, NY 10461; Johns
Hopkins School of Medicine, Baltimore, MD, USA.

Received April 19, 2012; accepted May 16, 2012; Epub May 23, 2012; Published June 30, 2012

Abstract: Barrett’s esophagus, a pre-malignant condition that can lead to esophageal adenocarcinoma, is characterized by histological
changes in the normal squamous epithelium of the esophagus. Numerous molecular changes occur during the multistage conversion of
Barrett’s metaplasia to dysplasia and frank adenocarcinoma. Epigenetic changes, especially changes in DNA methylation are widespread
during this process. Aberrant DNA methylation has been shown to occur at promoters of tumor suppressor genes, adhesion molecules and
DNA repair genes during Barrett’s esophagus. These epigenetic alterations can be used as molecular biomarkers for risk stratification and
early detection of esophageal adenocarcinoma. We also show that genome wide analysis of methylation surprisingly reveals that global
hypomethylation and not hypermethylation is the dominant change during Barrett’s metaplasia. The transformation of Barrett’s esophagus to
frank adenocarcinoma is in turn characterized by much smaller wave of selective promoter hypermethylation. These studies reveal many novel,
potential targets for new therapies and illustrate the utility of incorporating these epigenetic changes as biomarkers during endoscopic
surveillance interval for patients with Barrett’s esophagus.

Keywords: Barrett’s esophagus, DNA methylation, esophageal adenocarcinoma, global hypomethylation

Address all correspondence to:
Dr. Amit Verma
Albert Einstein College of Medicine
1300 morris park ave, C302B, Bronx, NY, USA.
Tel: 718-430-8761; Fax: 718-430-8702
E-mail: amit.verma@einstein.yu.edu