RB1 and astrocytoma (excluding glioblastoma): After reviewing the literature on multiple potential prognostic biomarkers, including CDKN2A/B HD, other Rb pathway genes, PIK3R1 and PIK3CA mutations, PDGFRA and MYCN amplification, reduced global DNA methylation, genomic instability (high copy number variants or somatic mutations), and mitotic activity and proliferation indices, they concluded that while “significant mitotic activity” should remain as a criterion for distinguishing grade 3 from grade 2 IDH-mutant astrocytomas, if CDKN2A/B HD, necrosis, or microvascular proliferation was present, a grade 4 designation was appropriate [7].