Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma

Andrew M Kaz; William M Grady; Matthew D Stachler; Adam J Bass

doi:10.1016/j.gtc.2015.02.015

Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma

Gastroenterol Clin North Am. 2015 Jun;44(2):473-89. doi: 10.1016/j.gtc.2015.02.015. Epub 2015 Apr 1.

Authors

Andrew M Kaz¹, William M Grady², Matthew D Stachler³, Adam J Bass⁴

Affiliations

¹ R&D Department, VA Puget Sound Health Care System, 1660 South Columbian Way, S-111-Gastro, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA, USA; Department of Internal Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
² Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA, USA; Department of Internal Medicine, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA. Electronic address: [email protected].
³ Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.

Abstract

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), wherein normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. BE can progress to low- and high-grade dysplasia, intramucosal, and invasive carcinoma. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Given the limitations of histopathology, genomic and epigenomic analyses may improve the precision of risk stratification. Assays to detect molecular alterations associated with neoplastic progression could be used to improve the pathologic assessment of BE/EAC and to select high-risk patients for more intensive surveillance.

Keywords: Aneuploidy; Barrett’s esophagus; Cancer genomics; DNA methylation; Esophageal adenocarcinoma; Genomic instability; LOH.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Aneuploidy
Barrett Esophagus / genetics*
Barrett Esophagus / pathology
DNA Methylation*
Epigenesis, Genetic*
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / pathology
Gene Dosage
Humans
MicroRNAs / genetics
Prognosis
Risk Assessment

Substances

MicroRNAs

Abstract

Publication types

MeSH terms

Substances

Grants and funding