该课题组人员对来自70个个体的142个组织进行了深度测序，包括肿瘤、肿瘤周围皮层或脑室下区和血液。37.9%的患者（29例中的11例）在肿瘤周围皮层发现低水平的IDH突变。结合细胞类型特异性突变分析、克隆进化方向、来自患者大脑的空间转录组学以及由突变的少突胶质细胞祖细胞引起的癌症主题模型，该研究组确定具有初始IDH突变的胶质祖细胞负责IDH突变胶质瘤的发展。
据悉，识别包含初始驱动突变的细胞起源是理解肿瘤进化和开发新疗法的关键。异柠檬酸脱氢酶（IDH）突变型胶质瘤是年轻人中最常见的原发性恶性脑肿瘤，其起源细胞目前尚不清楚。
附：英文原文
Title: IDH-mutant gliomas arise from glial progenitor cells harboring the initial driver mutation
Author: 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
Issue&Volume: 2026-01-08
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.
DOI: adt0559
Source: https://www.science.org/doi/10.1126/science.adt0559