Aberrant DNA methylation and Cancer

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Normal cells have genes that promote cell proliferation (oncogenes) and those that repress cell proliferation (tumor-suppressor genes). Distortion of genetic information (mutation) of oncogenes can result in constitutive activation of the oncogenes. In contrast, mutations of tumor-suppressor genes and also their deletion (chromosome deletion) result in their inactivation (Fig.). Both oncogene activation and tumor-suppressor gene inactivation can cause uncontrolled cellular proliferation.

In the 1990's, it was revealed that aberrant DNA methylation, in addition to mutations and chromosome deletion, can cause inactivation of tumor-suppressor genes (Ushijima, 2005). Until now, inactivation of many tumor-suppressor genes by aberrant DNA methylation was reported in various cancers. In some cancers such as gastric cancer, inactivation of tumor-suppressor genes by DNA methylation is more frequent than that by mutations or chromosome deletion (Ushijima and Sasako, 2004).


Fig. Three mechanisms of inactivation of tumor-suppressor genes.
Mutations, chromosome deletion, and aberrant DNA methylation are known as mechanisms for inactivation of tumor-suppressor genes. Aberrant DNA methylation causes inactivation of tumor-suppressor genes without any changes of genetic information of tumor-suppressor genes.