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Genetic and epigenetic inactivation of tumor-suppressor genes (TSGs). Mutations lead to inactivation of one allele of tumor-suppressor gene resulting in partial loss-of-function. The first hit highlights the event leading to partial loss of gene expression of the TSG. The selection pressure then could promote the second hit resulting in epugenetically-driven complete loss-of-function. The inactivity of TSG leads to tumorigenesis.
