Methylomics and cancer: the current state of methylation profiling and marker development for clinical care

Epigenetic modifications have long been recognized as an essential level in transcriptional regulation linking behavior and environmental conditions or stimuli with biological processes and disease development. Among them, methylation is the most abundant of these reversible epigenetic marks, predominantly occurring on DNA, RNA, and histones. Methylation modification is intimately involved in regulating gene transcription and cell differentiation, while aberrant methylation status has been linked with cancer development in several malignancies. Early detection and precise restoration of dysregulated methylation form the basis for several epigenetics-based therapeutic strategies. In this review, we summarize the current basic understanding of the regulation and mechanisms responsible for methylation modification and cover several cutting-edge research techniques for detecting methylation across the genome and transcriptome. We then explore recent advances in clinical diagnostic applications of methylation markers of various cancers and address the current state and future prospects of methylation modifications in therapies for different diseases, especially comparing pharmacological methylase/demethylase inhibitors with the CRISPRoff/on methylation editing systems. This review thus provides a resource for understanding the emerging role of epigenetic methylation in cancer, the use of methylation-based biomarkers in cancer detection, and novel methylation-targeted drugs.