Histone H3.3 G34-mutant Diffuse Gliomas in Adults. (5th August 2021)

• Record Type: Journal Article
• Authors: Wang, Leiming; Shao, Liwei; Li, Hainan; Yao, Kun; Duan, Zejun; Zhi, Cheng; Song, Shuangshuang; Cheng, Ye; Wang, Fuyu; Wang, Wei; Piao, Yueshan; Gui, Qiuping; Lu, Dehong; Qi, Xueling; Teng, Lianghong
• Is Part Of: American journal of surgical pathology. Volume 46:Number 2(2022)
• Page Start: 249
• Page End: 257
• Publication Date: 2021-08-05
• Subjects: glioma -- H3.3 G34R/V -- adult -- IDH -- next-generation sequencing; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001781
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : The characteristics of H3.3 G34-mutant gliomas in adults have yet to be specifically described. Thirty adults with H3.3 G34-mutant diffuse gliomas were retrospectively reviewed for clinical and pathologic information. Molecular profiling using next-generation sequencing was performed in 29 of the 30 H3.3 G34-mutant patients with 1 patient lacking available tumor samples, as well as 82 IDH/H3 wild-type adult diffuse glioma patients. The age at diagnosis of H3.3 G34-mutant diffuse gliomas was significantly younger than IDH/H3 wild-type gliomas (24 vs. 57 y, P <0.001). Overall, 19 of the 30 patients were diagnosed of glioblastoma with the primitive neuronal component, and 8 were glioblastoma. The molecular profiling analysis revealed higher frequencies of Olig-2 loss of expression, TP53 mutation, ATRX mutation, PDGFRA mutation, and MGMT promoter methylation ( P <0.05) in H3.3 G34-mutant gliomas than IDH/H3 wild-type gliomas. No TERT promoter mutation and only 1 case of EGFR amplification were detected in the H3.3 G34-mutant cohort, the frequencies of which were significantly higher in the IDH/H3 wild-type cohort. A dismal prognosis was observed in H3.3 G34-mutant patients comparing to IDH/H3 wild-type cohort (overall survival: 14 vs. 22 mo; P =0.026). Univariate and multivariate analyses showed that the extent of resection and TP53 mutation were independently affecting prognosis. The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.