CpG islands in hypermethylated tumor suppressor gene promoters (CGI)

CpG islands are genomic regions characterized by a high frequency of cytosine-guanine dinucleotide sequences, typically found within or near the promoter regions of approximately 70% of human genes (Herman & Baylin, 2003, NEJM). In healthy cells, these islands are generally unmethylated, allowing for active gene transcription. However, in many types of cancer, these regions undergo aberrant hypermethylation, a process mediated by DNA methyltransferases (DNMTs) that leads to the stable transcriptional silencing of tumor suppressor genes (Baylin & Jones, 2011, Nature Reviews Cancer). This epigenetic silencing is a hallmark of oncogenesis, contributing to the loss of cell cycle control, DNA repair, and apoptosis (NIH/NCI). Therapeutic intervention focuses on the use of hypomethylating agents, such as azacitidine and decitabine, which inhibit DNMTs to reverse methylation and restore the expression of these critical genes (PubMed). The clinical success of these agents in treating myelodysplastic syndromes and certain leukemias highlights the importance of targeting these genomic features to reverse the malignant phenotype.

Other names

CpG islandsCGIHypermethylated tumor suppressor gene promotersDNA methylation sitesCpG island methylator phenotypeCIMP

DNA methyltransferase inhibition leading to DNA hypomethylation and reactivation of silenced tumor suppressor genes.