IDH-mutant gliomas are the most common type of malignant brain tumor in young adults and are caused by mutations in the isocitrate dehydrogenase (IDH) genes. The study analyzed 142 tissues from 70 subjects (including tumors, surrounding cortex, subventricular zone and blood) by deep sequencing. In approximately 38% of IDH-mutant glioma patients (11 of 29), a low-level IDH1 mutation was found in the surrounding cortex outside the primary tumor, without additional tumor mutations.[1] An integrated analysis of mutations by cell type, clonal evolution, and spatial transcriptomics showed that glial progenitor cells, including oligodendrocyte progenitor cells, appear normal at the histological level to carry the initial IDH mutation.[1] In mouse models, where these progenitor cells were genetically engineered to carry an Idh mutation, their clonal expansion, the gradual acquisition of additional driver mutations, and the formation of IDH-mutant gliomas occurred.[1] Tumors generated in these models mimicked the histological structure and single-cell transcriptomic profiles of human IDH-mutant gliomas.[1] The main finding is that IDH-mutant gliomas arise from glial progenitor cells in the surrounding cerebral cortex, which first acquire an initial IDH mutation and only subsequently other tumor mutations leading to a fully developed tumor.[1]