Analyses of large cohorts of patients with IDH-mutant astrocytoma grades 2–4 have shown that CDK4 amplification is associated with shorter survival on multivariate analysis.88,90 Other studies have concluded that CDK4 amplification, when considered by itself, was not associated with poor prognosis on univariate analysis.75,91 Since CDK4 is a member of the RB pathway (Figure 1) and its amplification is mutually exclusive with CDKN2A/B homozygous deletion and RB1 mutation, some investigators have explored alterations of RB pathway members as a single risk factor. The gene discussed is CDK4; the disease is astrocytoma (excluding glioblastoma).