title: Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus.
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.
  
  
  CONCLUSIONS
  B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples.
  
  
  CONCLUSIONS
  These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Rachele M
authors.initials: RM
authors.lastname: O'Leary
authors.affiliation: Research and Development Service, VA Puget Sound Health Care System, Seattle, Washington. Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaz
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Shelli M
authors.initials: SM
authors.lastname: Morris
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Carter
authors.affiliation: Division of Gastroenterology, University Hospitals Case Medical Center, Cleveland, Ohio. Division of Oncology, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.affiliation: Division of Gastroenterology, University Hospitals Case Medical Center, Cleveland, Ohio. Division of Oncology, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Apoorva
authors.initials: A
authors.lastname: Chandar
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Moinova
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Cleveland, Ohio. Case Comprehensive Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.affiliation: University of Michigan Medical Center, Ann Arbor, Michigan.
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.affiliation: Department of Medicine and Gastroenterology, Baylor College of Medicine, Houston, Texas.
authors.forename: Sharmila
authors.initials: S
authors.lastname: Anandabapasathy
authors.affiliation: Department of Anatomic Pathology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Maria
authors.initials: M
authors.lastname: Westerhoff
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Chao-Jen
authors.initials: CJ
authors.lastname: Wong
authors.affiliation: Division of Gastroenterology & Hepatology, University of North Carolina Hospitals, Chapel Hill, North Carolina.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaheen
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, School of Medicine, Cleveland, Ohio.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Medicine, University of Washington School of Medicine, Seattle, Washington. wgrady@fredhutch.org.
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
mesh_terms: D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C475472:B3GAT2 protein, human; D014453:Glucuronosyltransferase