Role Of Dna Hypermethylation In Tumorigenesis

The CpG islands of a number of genes that are usually nonmethylated in normal cell types undergo methylation in a variety of human tumors.28 Methylation of CpG islands leads to inactivation or complete loss of expression and silencing of tumor suppressor genes involved in the determination of tumor cell phenotype. Transcriptional silencing and functional inactivation of tumor suppressor genes due to DNA hypermethylation provides an advantage of selective growth to neoplastic cells over normal cell types. DNA hypermethylation resulting in loss of transcriptional activity and function of a number of tumor-associated genes has been strongly implicated in malignant transformation (Table 2.1).

The promoter region of the p15INK4B tumor suppressor gene is commonly hypermethylated in gliomas and to some extent in leukemia, leading to the loss of its transcriptional activity.7

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