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How promoter hypermethylation contributes to dysregulation of a tumor suppressor gene (Tsp). As shown in this diagram, one of the wild-type Tsp alleles of a normal cell gets deactivated (Hit 1) through mutation (Tsp*), copy loss, or promoter hypermethylation. It may then be necessary to deactivate the second allele (Hit 2) for the Tsp to attain its tumor promoting state. As shown in this model, the deactivation of the second allele may also be attained by promoter hypermethylation.
