Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus
Year: 2015
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines. The development of noninvasive and accurate BE detection assays could potentially identify many of these undiagnosed BE patients. METHODS: DNA methylation is a common epigenetic alteration in BE. Therefore, we conducted a genome-wide methylation screen to identify potential BE biomarkers. Samples from SQ (N = 12), stomach (N = 28), and BE (N = 29) were analyzed and methylation levels at over 485,000 CpG sites were compared. Pyrosequencing assays were used to validate the results and MethyLight assays were developed to detect the methylated alleles in endoscopic brushings. RESULTS: We discovered two genes, B3GAT2 and ZNF793, that are aberrantly methylated in BE. Clinical validation studies confirmed B3GAT2 and ZNF793 methylation levels were significantly higher in BE samples (median = 32.5% and 33.1%, respectively) than in control tissues (median = 2.29% and 2.52%, respectively; P < 0.0001 for both genes). Furthermore, gene-specific MethyLight assays could accurately detect BE (P < 0.0001 for both) in endoscopic brushing samples. CONCLUSION: B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples. IMPACT: These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE.
Authors: Ming Yu, Rachele M. O'Leary, Andrew M. Kaz, Shelli M. Morris, Kelly T. Carter, Amitabh Chak, Apoorva Chandar, Joseph E. Willis, Helen R. Moinova, Sanford D. Markowitz, Dean E. Brenner, Sharmila Anandabapasathy, Maria Westerhoff, Chao-Jen Wong, Nicholas J. Shaheen, Yanwen Chen, Jill S. Barnholtz-Sloan, William M. Grady
Institutions: Fred Hutch Cancer Center, University of Washington, VA Puget Sound Health Care System, University Hospitals of Cleveland, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University, University of Michigan, Michigan Medicine, Baylor College of Medicine, University of North Carolina at Chapel Hill, University of North Carolina Hospitals
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Genetic Determinants of Barrett's Esophagus and Esophageal Adenocarcinoma, Non-Endoscopic Surveillance for Barrett's Esophagus Following Ablative Therapy, G4259426110, Biomarkers for Reducing Mortality of Cancers of the Colon and Esophagus, Esophageal Cancer from Cells to Population: A Multiscale Approach, San Antonio Center for Biomarkers of Risk for Prostate Cancer (SABOR), Case GI SPORE, The Cleveland Digestive Diseases Research Core Center (DDRCC), Cancer Center Support Grant, Great Lakes New England Clinical Validation Center, University of Washington GI Training Grant
OpenAlex ID: W2112659260