IDH-mutant gliomas generally arise in the cerebral cortex with only rare exceptions in posterior fossa structures or spinal cord, in contrast to tumors defined by other drivers, including H3 K27M-mutant diffuse midline gliomas, and different progenitor cells may be more susceptible to malignant transformation by mutually exclusive oncogenic drivers [111, 199]. The gene discussed is IDH2; the disease is central nervous system cancer.