AKT1 and astrocytoma (excluding glioblastoma): NF1 has been considered a mutational hot spot in the human genome.38 Germline mutations and loss-of-function mutations have been seen in the disease, which includes optic nerve gliomas, astrocytomas, and GBMs.45–47NF1 negatively regulates Ras as an exchange factor converting Ras-GTP to Ras-GDP by its GTPase-activating (Ras-GAP) domain.38 Ras-GTP is downstream of growth factor receptors at a major signal transduction crossroad, translating extrinsic messages into the Raf-MAPKK-ERK pathway or into either the PI3K-PKB or the PI3K-Rac-Rho pathway.