Much like IDH1/2 mutations, improved understanding of epigenetic dysregulation in glioma has led to the discovery of mutations encoding a lysine to methionine substitution at position 27 in histone H3 (H3K27M), which leads to the formation of high-grade gliomas, especially diffuse midline gliomas in children [175,176,177]. The gene discussed is IDH1; the disease is central nervous system cancer.