Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)382-396
Number of pages15
JournalInternational Journal of Clinical and Experimental Pathology
Volume5
Issue number5
StatePublished - 2012

Fingerprint

Barrett Esophagus
Epigenomics
Adenocarcinoma
DNA Methylation
Biomarkers
Tumor Suppressor Genes
DNA Repair
Methylation
Esophagus
Epithelium
Genome
Genes

Keywords

  • Barrett's esophagus
  • DNA methylation
  • Esophageal adenocarcinoma
  • Global hypomethylation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. / Agarwal, Archana; Polineni, Rahul; Hussein, Zulfiqar; Vigoda, Ivette; Bhagat, Tushar D.; Bhattacharyya, Sanchari; Maitra, Anirban; Verma, Amit.

In: International Journal of Clinical and Experimental Pathology, Vol. 5, No. 5, 2012, p. 382-396.

Research output: Contribution to journalArticle

@article{629f3a540cc44ce8b4f55a7c6a68ec94,
title = "Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma",
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",
author = "Archana Agarwal and Rahul Polineni and Zulfiqar Hussein and Ivette Vigoda and Bhagat, {Tushar D.} and Sanchari Bhattacharyya and Anirban Maitra and Amit Verma",
year = "2012",
language = "English (US)",
volume = "5",
pages = "382--396",
journal = "International Journal of Clinical and Experimental Pathology",
issn = "1936-2625",
publisher = "e-Century Publishing Corporation",
number = "5",

}

TY - JOUR

T1 - Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma

AU - Agarwal, Archana

AU - Polineni, Rahul

AU - Hussein, Zulfiqar

AU - Vigoda, Ivette

AU - Bhagat, Tushar D.

AU - Bhattacharyya, Sanchari

AU - Maitra, Anirban

AU - Verma, Amit

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Barrett's esophagus

KW - DNA methylation

KW - Esophageal adenocarcinoma

KW - Global hypomethylation

UR - http://www.scopus.com/inward/record.url?scp=84864312426&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864312426&partnerID=8YFLogxK

M3 - Article

C2 - 22808291

AN - SCOPUS:84864312426

VL - 5

SP - 382

EP - 396

JO - International Journal of Clinical and Experimental Pathology

JF - International Journal of Clinical and Experimental Pathology

SN - 1936-2625

IS - 5

ER -