RB1 and cancer: The pivotal p53 and retinoblastoma (RB) cell cycle control pathways were frequently incapacitated by the disruption of the Cdkn2a locus, which encodes two different tumor suppressors, the Cdk4 kinase inhibitor p16INK4a and the Mdm2-p53 regulator p19ARF, both of which play an important role in the development and progression of many human cancer types.