Journal Club: IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation

Science

8 Jan 2026

Vol 391, Issue 6781

Editor’s summary

Gliomas with mutations in the gene isocitrate dehydrogenase (IDH) are the most common type of malignant brain tumor in young adults. The IDH mutation has been proposed to occur at an early stage of glioma development, but the precise “cell of origin” has yet to be identified. Park et al. report that glial progenitor cells (GPCs), including oligodendrocyte progenitor cells (OPCs), carry the earliest IDH mutation (see the Perspective by Mount and Suvà). Low-level IDH mutations were found in noncancerous brain regions of patients located relatively far from the tumor site. Using deep sequencing technology, spatial transcriptomics, and an OPC-based experimental glioma model, tumor evolution was traced back to the mutant progenitor cells. These findings suggest that GPCs with IDH mutations may be the cellular starting point for the development of IDH-mutant glioma. —Priscilla N. Kelly