title: Strategies for validation and testing of DNA methylation biomarkers.
abstract: DNA methylation is a stable covalent epigenetic modification of primarily CpG dinucleotides that has recently gained considerable attention for its use as a biomarker in different clinical settings, including disease diagnosis, prognosis and therapeutic response prediction. Although the advent of genome-wide DNA methylation profiling in primary disease tissue has provided a manifold resource for biomarker development, only a tiny fraction of DNA methylation-based assays have reached clinical testing. Here, we provide a critical overview of different analytical methods that are suitable for biomarker validation, including general study design considerations, which might help to streamline epigenetic marker development. Furthermore, we highlight some of the recent marker validation studies and established markers that are currently commercially available for assisting in clinical management of different cancers.
authors.affiliation: Health & Environment Department, Molecular Diagnostics, AIT Austrian Institute of Technology, Vienna, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Noehammer
authors.forename: Walter
authors.initials: W
authors.lastname: Pulverer
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Hassler
authors.forename: Manuela
authors.initials: M
authors.lastname: Hofner
authors.forename: Matthias
authors.initials: M
authors.lastname: Wielscher
authors.forename: Klemens
authors.initials: K
authors.lastname: Vierlinger
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
authors.forename: David
authors.initials: D
authors.lastname: McCarthy
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Jensen
authors.forename: Anders
authors.initials: A
authors.lastname: Nygren
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Geert
authors.initials: G
authors.lastname: Trooskens
authors.forename: Maarten
authors.initials: M
authors.lastname: Braspenning
authors.forename: Wim
authors.initials: W
authors.lastname: Van Criekinge
authors.forename: Gerda
authors.initials: G
authors.lastname: Egger
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinhaeusel
mesh_terms: D015415:Biomarkers; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods* / Q000592:standards*; D017408:Guidelines as Topic; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000235:genetics*; D054928:Validation Studies as Topic
chemical_list: D015415:Biomarkers
keywords: DNA methylation; MALDI; assay validation; biomarker; bisulfite-deamination; circulating free DNA; deep sequencing; pyrosequencing; qPCR