Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma.
10.1007/s11684-022-0936-z
- Author:
Jing FENG
1
;
Zheng ZHAO
2
;
Yanfei WEI
1
;
Zhaoshi BAO
3
;
Wei ZHANG
3
;
Fan WU
2
;
Guanzhang LI
2
;
Zhiyan SUN
2
;
Yanli TAN
4
;
Jiuyi LI
5
;
Yunqiu ZHANG
6
;
Zejun DUAN
7
;
Xueling QI
7
;
Kai YU
8
;
Zhengmin CONG
1
;
Junjie YANG
1
;
Yaxin WANG
1
;
Yingyu SUN
1
;
Fuchou TANG
8
;
Xiaodong SU
8
;
Chuan FANG
9
;
Tao JIANG
10
;
Xiaolong FAN
11
Author Information
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. chuanfang@hbu.edu.cn.
10. Beijing Neurosurgical Institute, Beijing, 100070, China. taojiang1964@163.com.
11. Beijing Key Laboratory of Gene Resource and Molecular Development, Laboratory of Neuroscience and Brain Development, Beijing Normal University, Beijing, 100875, China. xfan@bnu.edu.cn.
- Publication Type:Journal Article
- Keywords:
EM/PM subtyping;
glioma progression;
intratumor heterogeneity;
molecular classification
- MeSH:
Humans;
Brain Neoplasms/pathology*;
Neoplasm Recurrence, Local/metabolism*;
Glioma/pathology*;
Neural Stem Cells/pathology*;
Oligodendrocyte Precursor Cells/pathology*;
Tumor Microenvironment
- From:
Frontiers of Medicine
2023;17(2):240-262
- CountryChina
- Language:English
-
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.
