The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant Journal Article
| Authors: | Le Rhun, E.; Bink, A.; Felsberg, J.; Gramatzki, D.; Brandner, S.; Benhamida, J. K.; Wick, A.; Tonn, J. C.; Mohme, M.; Tabatabai, G.; Capper, D.; Snuderl, M.; Razis, E.; Ronellenfitsch, M. W.; Neidert, N.; Ng, H. K.; Pohl, U.; Bale, T.; Quach, S.; Rieger, D.; Schüller, U.; Onken, J.; Drüschler, K.; Maurage, C. A.; Regli, L.; Healy, E.; Graham, M.; Hortobagyi, T.; Paine, S.; Bridges, L.; Lausova, T.; Medici, V.; Sievers, P.; Schrimpf, D.; Wick, W.; Sahm, F.; Reifenberger, G.; von Deimling, A.; Weller, M.; for the H3 G34 DHG Study Group |
| Article Title: | The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant |
| Abstract: | Background 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. Methods 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. Results 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. Conclusions 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. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | immunohistochemistry; adolescent; adult; child; human tissue; preschool child; school child; aged; child, preschool; middle aged; survival rate; retrospective studies; young adult; gene sequence; major clinical study; methylation; overall survival; genetics; missense mutation; mutation; cancer radiotherapy; temozolomide; neuroimaging; nuclear magnetic resonance imaging; brain tumor; follow up; glioma; brain neoplasms; follow-up studies; cancer grading; edema; progression free survival; tumor volume; radiotherapy dosage; cohort analysis; genetic variability; pathology; retrospective study; necrosis; protein p53; tumor marker; dna methylation; karnofsky performance status; histone; multicenter study; glioblastoma; histone h3; mitosis rate; oligodendroglioma; methylated dna protein cysteine methyltransferase; cyclin dependent kinase inhibitor 2a; gene dosage; chromosome loss; astrocytoma; diffusion weighted imaging; histones; dna helicase; neuropathology; calcification; chromosome 10q; isocitrate dehydrogenase; chromosome 7; dna copy number variations; cyclin dependent kinase 6; copy number variation; chromosome 9q; chromosome 10; mgmt; cyclin dependent kinase inhibitor 2b; methylome; apparent diffusion coefficient; loss; cancer prognosis; sanger sequencing; dna sequencing; humans; prognosis; human; male; female; article; median survival time; droplet digital polymerase chain reaction; biomarkers, tumor; transcriptional regulator atrx; t2 weighted imaging; t1 weighted imaging; fluid-attenuated inversion recovery imaging; diffuse hemispheric glioma; werner syndrome atp dependent helicase; h3-3a protein, human; h3 g34 mutant |
| Journal Title: | Neuro-Oncology |
| Volume: | 27 |
| Issue: | 6 |
| ISSN: | 1522-8517 |
| Publisher: | Oxford University Press |
| Date Published: | 2025-06-01 |
| Start Page: | 1519 |
| End Page: | 1535 |
| Language: | English |
| DOI: | 10.1093/neuonc/noaf015 |
| PUBMED: | 39842935 |
| PROVIDER: | scopus |
| PMCID: | PMC12309718 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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