RB1 and diffuse astrocytoma: Attempts to molecularly define the aggressive type of diffuse astrocytomas have suggested several genetic markers such as RB1 pathway alterations (e.g., CDKN2A/B homozygous deletion or CDK4 amplification), PIK3R1 mutation, PDGFRA amplification, or G-CIMP low type in the methylation cluster [2, 3, 7, 11, 21, 25].