DNA methylation based biomarkers: Practical considerations and applications

A biomarker is a molecular target analyzed in a qualitative or quantitative manner to detect and diagnose the presence of a disease, to predict the outcome and the response to a specific treatment allowing personalized tailoring of patient management. Biomarkers can belong to different types of biochemical molecules such as proteins, DNA, RNA or lipids, whereby protein biomarkers have been the most extensively studied and used, notably in blood-based protein quantification tests or immunohistochemistry. The rise of interest in epigenetic mechanisms has allowed the identification of a new type of biomarker, DNA methylation, which is of great potential for many applications. This stable and heritable covalent modification mostly affects cytosines in the context of a CpG dinucleotide in humans. It can be detected and quantified by a number of technologies including genome-wide screening methods as well as locus- or gene-specific high-resolution analysis in different types of samples such as frozen tissues and FFPE samples, but also in body fluids such as urine, plasma, and serum obtained through non-invasive procedures. In some cases, DNA methylation based biomarkers have proven to be more specific and sensitive than commonly used protein biomarkers, which could clearly justify their use in clinics. However, very few of them are at the moment used in clinics and even less commercial tests are currently available. The objective of this review is to discuss the advantages of DNA methylation as a biomarker, the practical considerations for their development, and their use in disease detection, prediction of outcome or treatment response, through multiple examples mainly focusing on cancer, but also to evoke their potential for complex diseases and prenatal diagnostics.