Conversely, loss of the endogenous CDK4/6 inhibitors (CDKN2A, CDKN2B, CDKN2C, and CDKN2D) or RB-family (RB1, RBL2, and RBL1) are also observed in specific tumor settings (Fig. 1b and Supplementary Fig. 2), in total the RB-pathway is subject to genetic perturbation in greater than 30% of tumors. Here, CDK4 is linked to neoplasm.