A predisposing germline mutation in the NF1 gene often progresses to homozygosity, with the somatic mutation burden in NF1-associated gliomas being modulated by both age and tumor grade. High-grade tumors exhibit genetic modifications in TP53 and CDKN2A, alongside prevalent mutations in ATRX that are associated with the ALT phenotype. Furthermore, these tumors demonstrate an enrichment of genetic alterations affecting transcription/chromatin regulation and the PI3K pathways. Here, CDKN2A is linked to central nervous system cancer.