DNA methylation biomarkers (DNAm)

DNA methylation biomarkers represent specific patterns of 5-methylcytosine (5mC) modifications on DNA, primarily occurring at CpG dinucleotides, which serve as indicators of biological or pathological states. These biomarkers are essential for regulating gene expression, as hypermethylation of promoter regions typically leads to transcriptional silencing, while hypomethylation can lead to gene activation (NIH, 2023). In the context of disease, particularly oncology, aberrant DNA methylation is a hallmark of cancer development, often involving the silencing of tumor suppressor genes (PubMed, PMID: 31036103). Clinical applications of these biomarkers include the use of MGMT promoter methylation to predict response to alkylating agents in glioblastoma and SEPT9 methylation for colorectal cancer screening (StatPearls, 2024). While the biomarkers themselves are diagnostic or prognostic tools, the enzymes responsible for these modifications, such as DNA methyltransferases (DNMTs), are the actual therapeutic targets. Drugs like azacitidine and decitabine function by inhibiting DNMTs, thereby inducing DNA hypomethylation and potentially restoring the expression of silenced genes. However, the use of these agents is associated with challenges such as non-specific gene activation and systemic toxicity, including myelosuppression (Wikipedia, 2024).

Other names

Epigenetic biomarkersCpG methylation markersDNA methylation signaturesMethylation markers

DNA methyltransferase (DNMT) inhibition leading to DNA hypomethylation and reactivation of silenced genes (StatPearls, 2024).