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

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 <i>IDH</i> 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 <i>IDH</i> mutation were responsible for the development of IDH-mutant gliomas.

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Publication Details

Journal
Science
Published
2026-01-08
DOI
https://doi.org/10.1126/science.adt0559
Citations
4
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
147.73
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article

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

Chungyeul Kim, Keon Woo Kim, Jung Won Park, Jihwan Yoo et al.
4 citations
Science
Glioma Diagnosis and Treatment
147.73
article

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

Chungyeul Kim, Keon Woo Kim, Jung Won Park, Jihwan Yoo, ST Jung, Stefan Pusch, Eui-hyun Kim, Sang Mee Lee, Jeong Ho Lee, Jiehoon Kwak, Kang Ss, Sangjeong Ahn, Jin-Kyoung Shim, Ji-Hyung Park, Chang Hyun Nam, Se Hoon Kim, Jong Hee Chang, Andreas von Deimling, Hyun Jung Kim, Hye Joung Cho, Yongjin Ahn, Chanho Choi
article en
4 citations

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 <i>IDH</i> 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 <i>IDH</i> mutation were responsible for the development of IDH-mutant gliomas.

ScienceVol. 391(6781)
Korea Advanced Institute of Science and Technology (KR), German Cancer Research Center (DE), Yonsei University (KR), Korea University (KR), Heidelberg University (DE), Severance Hospital (KR), University Hospital Heidelberg (DE), Hopp Children's Cancer Center Heidelberg (DE), Gangnam Severance Hospital (KR), Korea University (JP), Orano (United States) (US), Sungkyunkwan University (KR)
Openalex Percentile: Top 0%
Glioma Diagnosis and Treatment
147.73
DOISourceOpenAlex
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