Diffuse Isocitrate Dehydrogenase–Mutant Gliomas With Histone H3 Alterations Are Distinguished by Unique Clinical Characteristics, Molecular Expression Profile, and Survival Prognosis

Abstract

BACKGROUND AND OBJECTIVES: Histopathological 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). METHODS: A 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. RESULTS: Diffuse 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. CONCLUSION: Identification and assessment of histone H3 status in clinical practice might help improve prognostic prediction and develop therapeutic strategies for these patient subgroups.

Letter: Diffuse Isocitrate Dehydrogenase-Mutant Gliomas With Histone H3 Alterations are Distinguished by Unique Clinical Characteristics, Molecular Expression Profile, and Survival Prognosis

“…We read with significant inquisitive the article published in Neurosurgery by Cheng et al, 1 which investigated the clinical characteristics, molecular phenotypes, and survival prognosis of gliomas with histone H3 abnormalities (H3 alterations) in isocitrate dehydrogenase (IDH)-mutant (IDHmt) patients. Diffuse IDH-mutant gliomas with H3 changes are characterized by particular clinical traits, molecular expression profiles, and survival prognosis, which they categorized as a potentially important discovery.…”

“…However, a deeper analysis of the biology using bioinformatics technologies of H3 alterations is required for a more precise assessment of the clinical significance. 1 The novel creation of multicenter prospective studies with larger samples and appropriate clinical and imaging parameter annotation can be advised. In addition to the scholarly debate that is sparked, it is important to learn from the findings of such study because treating these complex glioma patients is not a simple task.…”