CDK4 and glioblastoma: This locus encodes an additional tumor suppressor protein in p16INK4a that inhibits cyclin D to bind cyclin-dependent kinase 4 and 6, preventing the complex to phosphorylate Rb and to promote G1 to S phase transition.28,29 Thus, CDKN2A deletion promotes tumorigenesis via 2 of the central somatic mutation pathways implicated in GBM pathogenesis and is typically occurring in the presence of CDKN2B deletion.