MGMT and astrocytoma (excluding glioblastoma): Univariate analysis, performed on three combined cohorts of publicly available IDH-mutant astrocytoma cases (n = 518) [17, 38, 104], demonstrated a significantly detrimental effect of increasing histologic grade (p < 0.0001), homozygous CDKN2A deletion (p < 0.0001), CDK4 amplification (p < 0.0001), CCND2 amplification (p < 0.0001), chromosomal instability (p < 0.0001), MMR mutation (p = 0.0003), and subclonality of IDH1 mutation (p = 0.0457), while MGMT promoter methylation was not significantly associated with patient survival (Fig. 5a).