CDKN2A and central nervous system cancer: (4) The cell cycle progression machinery: Critical regulators of cell growth are frequently mutated in human gliomas, including the tumor suppressor retinoblastoma (pRB), CDK4 (activating mutations) and CDKN2A (inactivating mutations) with consequent overexpression of MDM2, an inhibitor of the tumor suppressor protein ARF (p14ARF).