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

Science 2026

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Authors: Jung Won Park, Jiehoon Kwak, Keon Woo Kim, ST Jung, Chang Hyun Nam, Hyun Jung Kim, Sang Mee Lee, Chanho Choi, Yongjin Ahn, Ji-Hyung Park, Jihwan Yoo, Jin‐Kyoung Shim
+12 more 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, Kang Ss, Jeong Ho Lee
DOI: 10.1126/science.adt0559
Cited by: 14
References: 112

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.

Fields of Study & Subjects

Glioma Diagnosis and Treatment Cancer Genomics and Diagnostics Neurofibromatosis and Schwannoma Cases

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
391
Issue
6781
Pages
eadt0559–eadt0559
Publication date
8 January 2026
Language
EN