Developing DNA methylation-based diagnostic biomarkers

• Type of Material: Article
• Authors: Hye Kim, Emory University; Xudong Wang, Jilin University; Peng Jin, Emory University
• Language: English
• Date: 2018-02-20
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jgg.2018.02.003
• Title of Journal or Parent Work: Journal of Genetics and Genomics
• ISSN: 1673-8527
• Volume: 45
• Issue: 2
• Start Page: 87
• End Page: 97
• Grant/Funding Information: This work was supported in part by NIH grants (NS051630, NS079625, MH102690 and NS097206 to P.J.).
• Keywords: ALZHEIMERS-DISEASE; THERAPEUTIC STRATEGIES; Life Sciences & Biomedicine; OXYTOCIN RECEPTOR GENE; Biomarker; Molecular diagnosis; GENOME-WIDE ASSOCIATION; Liquid biopsy; CELL-FREE DNA; Biochemistry & Molecular Biology; PROSTATE-SPECIFIC ANTIGEN; Science & Technology; CPG ISLANDS; Brain disorders; PROMOTER REGION FLANKING; Epigenetics; Cancer; DNA methylation; PARKINSONS-DISEASE; BREAST-CANCER; Genetics & Heredity
• Research Categories: Chemistry, Biochemistry; Health Sciences, Oncology; Biology, Genetics

Abstract

An emerging paradigm shift for disease diagnosis is to rely on molecular characterization beyond traditional clinical and symptom-based examinations. Although genetic alterations and transcription signature were first introduced as potential biomarkers, clinical implementations of these markers are limited due to low reproducibility and accuracy. Instead, epigenetic changes are considered as an alternative approach to disease diagnosis. Complex epigenetic regulation is required for normal biological functions and it has been shown that distinctive epigenetic disruptions could contribute to disease pathogenesis. Disease-specific epigenetic changes, especially DNA methylation, have been observed, suggesting its potential as disease biomarkers for diagnosis. In addition to specificity, the feasibility of detecting disease-associated methylation marks in the biological specimens collected noninvasively, such as blood samples, has driven the clinical studies to validate disease-specific DNA methylation changes as a diagnostic biomarker. Here, we highlight the advantages of DNA methylation signature for diagnosis in different diseases and discuss the statistical and technical challenges to be overcome before clinical implementation.