Journal Article

DKFZ-2026-00072

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation.

Park, J. W. ; Kwak, J. ; Kim, K.-W. ; Jung, S. ; Nam, C. H. ; Kim, H. J. ; Lee, S. M. ; Choi, C. ; Ahn, Y. ; Park, J.-H. ; Yoo, J. ; Shim, J.-K. ; Cho, H. J. ; Kim, E.-H. ; Kim, C. ; Ahn, S. ; Pusch, S.DKFZ* ; von Deimling, A.DKFZ* ; Chang, J. H. ; Kim, S. H. ; Kim, H. ; Ju, Y. S. ; Kang, S.-G. ; Lee, J. H.

2026
American Association for the Advancement of Science Washington, DC

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.

Keyword(s): Isocitrate Dehydrogenase: genetics (MeSH) ; Glioma: genetics (MeSH) ; Glioma: pathology (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Brain Neoplasms: genetics (MeSH) ; Brain Neoplasms: pathology (MeSH) ; Mice (MeSH) ; Mutation (MeSH) ; Neuroglia: pathology (MeSH) ; Clonal Evolution (MeSH) ; Adult (MeSH) ; Female (MeSH) ; Male (MeSH) ; Isocitrate Dehydrogenase ; IDH1 protein, human

Note: #DKTKZFB26# / ISSN 1095-9203

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Contributing Institute(s):

1. KKE Neuropathologie (B300)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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