This hypothesis has potential implications to abrogate the establishment and progression of a malignant glioma recurrent phenotype, suggesting possible synergistic activity of an IDH mutant inhibitor (to target a phenotypic subpopulation of G-CIMP tumor cells with a tumorigenic advantage) combined with targeted therapy aimed at re-establishing the tumor suppressor gene function at CDKN2A and CDKN1B gene loci (to target a phenotypic subpopulation of G-CIMP tumor cells with tumor-propagating and tumor relapse advantages). Here, CDKN2A is linked to malignant glioma.