Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's esophagus.

Autor:	Moinova HR; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., LaFramboise T; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.; Department of Genetics and Genome Sciences, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Lutterbaugh JD; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Chandar AK; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Dumot J; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Faulx A; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Brock W; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., De la Cruz Cabrera O; Department of Mathematical Sciences, Kent State University, Kent, OH 44242, USA., Guda K; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA., Barnholtz-Sloan JS; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA., Iyer PG; Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA., Canto MI; Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA., Wang JS; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA., Shaheen NJ; Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Thota PN; Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Willis JE; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org.; Department of Pathology, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.; University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Chak A; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.; University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA., Markowitz SD; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. sxm10@cwru.edu josephe.willis@uhhospitals.org amitabh.chak@uhhospitals.org.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.; Department of Genetics and Genome Sciences, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.; University Hospitals Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2018 Jan 17; Vol. 10 (424).
DOI:	10.1126/scitranslmed.aao5848
Abstrakt:	We report a biomarker-based non-endoscopic method for detecting Barrett's esophagus (BE) based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma. Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve of 0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 min. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE. (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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