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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

Frontiers of Medicine  2023, Vol. 17 Issue (2): 240-262   https://doi.org/10.1007/s11684-022-0936-z
  本期目录
Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma
Jing Feng1, Zheng Zhao2, Yanfei Wei1, Zhaoshi Bao3, Wei Zhang3, Fan Wu2, Guanzhang Li2, Zhiyan Sun2, Yanli Tan4, Jiuyi Li5, Yunqiu Zhang6, Zejun Duan7, Xueling Qi7, Kai Yu8, Zhengmin Cong1, Junjie Yang1, Yaxin Wang1, Yingyu Sun1, Fuchou Tang8, Xiaodong Su8, Chuan Fang9(), Tao Jiang2,3,10(), Xiaolong Fan1,10()
1. Beijing Key Laboratory of Gene Resource and Molecular Development, Laboratory of Neuroscience and Brain Development, Beijing Normal University, Beijing 100875, China
2. Beijing Neurosurgical Institute, Beijing 100070, China
3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
4. Department of Pathology, Affiliated Hospital of Hebei University, Baoding 071000, China
5. Gendya Biotechnology Ltd., Beijing 100176, China
6. Center of Growth Metabolism & Aging, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China
7. Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China
8. Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China
9. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000, China; Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding 071000, China
10. Chinese Glioma Genome Atlas Network (CGGA), Beijing 100070, China
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Abstract

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Key wordsglioma progression    molecular classification    EM/PM subtyping    intratumor heterogeneity
收稿日期: 2022-01-11      出版日期: 2023-05-26
Corresponding Author(s): Chuan Fang,Tao Jiang,Xiaolong Fan   
 引用本文:   
. [J]. Frontiers of Medicine, 2023, 17(2): 240-262.
Jing Feng, Zheng Zhao, Yanfei Wei, Zhaoshi Bao, Wei Zhang, Fan Wu, Guanzhang Li, Zhiyan Sun, Yanli Tan, Jiuyi Li, Yunqiu Zhang, Zejun Duan, Xueling Qi, Kai Yu, Zhengmin Cong, Junjie Yang, Yaxin Wang, Yingyu Sun, Fuchou Tang, Xiaodong Su, Chuan Fang, Tao Jiang, Xiaolong Fan. Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma. Front. Med., 2023, 17(2): 240-262.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0936-z
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I2/240
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