Le Rhun Emilie, Bink Andrea, Felsberg Joerg, Gramatzki Dorothee, Brandner Sebastian, Benhamida Jamal K, Wick Antje, Tonn Joerg C, Mohme Malte, Tabatabai Ghazaleh, Capper David, Snuderl Matija, Razis Evangelia, Ronellenfitsch Michael W, Neidert Nicolas, Ng Ho-Keung, Pohl Ute, Bale Tejus, Quach Stefanie, Rieger David, Schüller Ulrich, Onken Julia, Drüschler Katharina, Maurage Claude-Alain, Regli Luca, Healy Estelle, Graham Maya, Hortobagyi Tibor, Paine Simon, Bridges Leslie, Lausova Tereza, Medici Valentina, Sievers Philipp, Schrimpf David, Wick Wolfgang, Sahm Felix, Reifenberger Guido, von Deimling Andreas, Weller Michael
Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Neuro Oncol. 2025 Jul 30;27(6):1519-1535. doi: 10.1093/neuonc/noaf015.
Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, has been newly defined in the 2021 World Health Organization (WHO) classification of central nervous system tumors. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors.
We retrospectively assembled a cohort of 114 patients (median age 22 years) with diffuse hemispheric glioma, H3 G34-mutant, central nervous system WHO grade 4, and profiled the imaging, histological, and molecular landscape of their tumors.
Compared with glioblastoma, H3 G34-mutant diffuse hemispheric gliomas exhibited less avid contrast enhancement, necrosis, and edema on MRI. Comprehensive analyses of mutational and DNA copy number profiles revealed recurrent mutations in TP53 and ATRX, homozygous deletions of CDKN2A/B, and amplifications of PDGFRA, EGFR, CCND2, and MYCN. MGMT promoter methylation was detected in 79 tumors (75%); 11 tumors (13%) showed DNA copy number profiles suggestive of circumscribed deletions on 10q26.3 involving the MGMT locus. Median survival was 21.5 months. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological, and molecular features, the absence of pial invasion and the presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses.
This study refines the clinical and molecular landscape of H3 G34-mutant diffuse hemispheric gliomas. Dedicated trials for this novel tumor type are urgently needed.
弥漫性半球胶质瘤，组蛋白3（H3）G34突变型，是2021年世界卫生组织（WHO）中枢神经系统肿瘤分类中新定义的肿瘤。在此，我们试图明确这些肿瘤的临床、神经影像学、病理及分子特征的预后作用。
我们回顾性纳入了114例弥漫性半球胶质瘤、H3 G34突变型、WHO中枢神经系统4级患者（中位年龄22岁），并对其肿瘤的影像学、组织学及分子特征进行了分析。
与胶质母细胞瘤相比，H3 G34突变型弥漫性半球胶质瘤在MRI上表现出对比度增强、坏死及水肿程度较低。对突变和DNA拷贝数图谱的综合分析显示，TP53和ATRX存在复发性突变，CDKN2A/B存在纯合缺失，PDGFRA、EGFR、CCND2和MYCN存在扩增。79例肿瘤（75%）检测到MGMT启动子甲基化；11例肿瘤（13%）的DNA拷贝数图谱显示10q26.3存在局限性缺失，累及MGMT基因座。中位生存期为21.5个月。单因素分析显示，女性、大体全切及MGMT启动子甲基化是阳性预后因素。在放射学、病理学及分子特征中，无软脑膜侵犯、存在微血管增生及CDK6扩增在单因素分析中是阳性预后因素。
本研究明确了H3 G34突变型弥漫性半球胶质瘤的临床及分子特征。迫切需要针对这种新型肿瘤类型开展专门试验。
