Abstract B047: IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation

Abstract Identifying the cell of origin that harbors an initial driver mutation is key to understanding tumor evolution and for the development of new treatments. For isocitrate dehydrogenase (IDH) –mutant gliomas, the most common malignant primary brain tumor in young adults, the cell of origin is currently poorly understood. We conducted deep sequencing on 142 tissues from 70 individuals comprising tumors, peritumoral cortex or subventricular zones, and blood. Low-level IDH mutations were found in the peritumoral cortex in 37. 9% (11 of 29) of patients. Integrating cell-type–specific mutation analysis, the direction of clonal evolution, spatial transcriptomics from patient brains, and a cancer mouse model arising from mutant oligodendrocyte progenitor cell, we determined that glial progenitor cells harboring an initial IDH mutation were responsible for the development of IDH-mutant gliomas. Citation Format: Jung Won Park, Jiehoon Kwak, Keon-Woo Kim, Saehoon Jung, Chang Hyun Nam, Hyun Jung Kim, Sang Mee Lee, Chanho Choi, Yongjin Ahn, Ji-Hyung Park, Jihwan Yoo, Jin-Kyoung Shim, Hye Joung Cho, Eui-Hyun Kim, Chungyeul Kim, Sangjeong Ahn, Stefan Pusch, Andreas von Deimling, Jong Hee Chang, Se Hoon Kim, Hoon Kim, Young Seok Ju, Seok-Gu Kang, Jeong Ho Lee. IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (6Suppl): Abstract nr B047.