Clinicopathological and molecular genetic characteristics of diffuse midline glioma with H3K27 alterations
10.13315/j.cnki.cjcep.2025.09.011
- VernacularTitle:弥漫性中线胶质瘤伴H3K27变异型的临床病理学及分子遗传学特征
- Author:
Juan DU
1
;
Yongqing LI
1
;
Wenli CUI
1
;
Liping SU
1
;
Wei ZHANG
1
;
Jing XUE
1
Author Information
1. 新疆医科大学第一附属医院病理科,乌鲁木齐 830000
- Publication Type:Journal Article
- Keywords:
diffuse midline gliomas;
H3K27 alteration;
clinicopathological characteristics;
next-generation sequencing
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(9):1187-1193
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the clinicopathological features,molecular subtypes,and prognostic factors of diffuse midline glioma(DMG)with H3K27 alterations.Methods Clinical data from 19 patients from DMG were col-lected.The clinical manifestations,histopathological features,immunophenotypes,and molecular genetic characteris-tics were analyzed.Relevant literature was also reviewed.Results Among the 19 patients,12 cases had tumors loca-ted in the thalamus,while 7 cases had tumors in other midline regions(including 4 cases in the brainstem,1 case in the cerebellum,and 2 cases in the spinal cord).Clinical symptoms primarily included dizziness,gait instability,and blurred vision.Histological features were diverse,with 12 cases classified as high-grade gliomas and 7 cases as low-grade.Immunohistochemistry revealed a loss of H3K27me3 expression in all cases,with 18 cases showing diffuse H3K27M positivity and 1 case expressing EZHIP.Of the 16 cases that underwent next-generation sequencing(NGS),1 case showed EGFR mutation(1/16,6％),while the remaining 15 cases had H3F3A K27M mutations(15/16,94％).Among these,7 cases had ATRX mutations(7/15,46.6％),5 cases had MAPK pathway alterations(5/15,33.3％,including 2 cases FGFR1,2 cases NF1,1 case co-mutated with BRAF and NF1),5 cases had PDGFRA mis-sense mutations(5/15,33.3％),4 cases had p53 missense or frameshift deletions(4/15,26.6％).One case each had a DICER1 missense mutation and an IDH1-S202R frameshift deletion(1/15,6.6％).The prognosis was general-ly poor,with a median survival of 9.5 months.Conclusion DMG exhibits high tumor heterogeneity and an overall poor prognosis.The predominant molecular aleration was the H3F3A K27M mutation.Patients with co-altered MAPK pathway showed relatively better outcomes,providing new insights into the molecular genetic characteristics of DMG.
