• Cheng Cheng, Di Wang, Mingchen Yu, You Zhai, Changqing Pan, Bo Liang, Jiazheng Zhang, Chen Wang, Yiyun Yin, Lianwang Li, Fan Wu, Zhongfang Shi, Xing Fan, Xing Liu, Zhiliang Wang, Zheng Zhao, Guanzhang Li, Tao Jiang, Wei Zhang, and Chinese Glioma Genome Atlas (CGGA) Network.
• Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing , China.
• Neurosurgery. 2023 Oct 1; 93 (4): 802812802-812.

Background And ObjectivesHistopathological features and molecular biomarkers have been studied as potential prognostic factors. This study aimed to investigate the clinical features, molecular phenotypes, and survival prognosis of isocitrate dehydrogenase (IDH)-mutant (IDHmt) gliomas with histone H3 alterations (H3-alterations).MethodsA total of 236 and 657 patients with whole-exome sequencing data were separately collected from the Chinese Glioma Genome Atlas and The Cancer Genome Atlas databases. Survival analysis of patients with glioma was performed using Kaplan-Meier survival curves stratified by histone H3 status. Univariate and multivariate analyses were used to identify the associations between histone H3 status and other clinicopathological factors with survival in patients with IDH-mutant gliomas.ResultsDiffuse gliomas with H3 alterations are more likely to be high grade in 2 cohorts ( P = .025 and P = .021, respectively). IDHmt glioma patients with H3-alteration had significantly less life expectancy than histone H3 wild-type ( P = .041 and P = .008, respectively). In the Chinese Glioma Genome Atlas cohort, Karnofsky performance scores ≤ 80 (HR 2.394, 95% CI 1.257-4.559, P = .008), extent of resection (HR 0.971, 95% CI 0.957-0.986, P < .001), high WHO grade (HR 6.938, 95% CI 2.787-17.269, P < .001), H3-alteration (HR 2.482, 95% CI 1.183-4.981, P = .016), and 1p/19q codeletion (HR 0.169, 95% CI 0.073-0.390, P < .001) were independently associated with IDHmt gliomas. In the The Cancer Genome Atlas cohort, age (HR 1.034, 95% CI 1.008-1.061, P = .010), high WHO grade (HR 2.365, 95% CI 1.263-4.427, P = .007), and H3-alteration (HR 2.501, 95% CI 1.312-4.766, P = .005) were independently associated with IDHmt gliomas.ConclusionIdentification and assessment of histone H3 status in clinical practice might help improve prognostic prediction and develop therapeutic strategies for these patient subgroups.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.

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