PATH-05. CLINICAL, PATHOLOGICAL AND MOLECULAR DISEASE CHARACTERISTICS OF DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT
Abstract BACKGROUND Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, is a pediatric-type diffuse high-grade glioma newly defined in the World Health Organization (WHO) classification of central nervous system tumors 2021. 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 with diffuse hemispheric glioma, H3 G34-mutant and profiled the imaging presentation and the molecular landscape of their tumors. RESULTS Compared with glioblastoma, H3 G34-mutant tumors exhibited less avid contrast enhancement, less necrosis and less 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 (95% CI 15.3-27.7) and eight patients (7.0%) survived for ≥ five years. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological and molecular features, absence of pial invasion, and presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses. CONCLUSION 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.
Authors
- J. C. Tonn (ORCID: https://orcid.org/0009-0004-1756-423X)
- Sebastian Brandner (ORCID: https://orcid.org/0000-0002-9821-0342)
- Guido Reifenberger (ORCID: https://orcid.org/0000-0002-1419-9837)
- Michael Ronellenfitsch (ORCID: https://orcid.org/0000-0002-1402-6290)
- Tejus Bale (ORCID: https://orcid.org/0000-0003-3641-9287)
- Michael Weller (ORCID: https://orcid.org/0000-0002-1748-174X)
- Nicolas Neidert (ORCID: https://orcid.org/0000-0003-0299-1138)
- Daniel Schrimpf (ORCID: https://orcid.org/0000-0003-3063-2423)
- Maya Srikanth Graham (ORCID: https://orcid.org/0000-0003-4748-974X)
- Valentina Medici (ORCID: https://orcid.org/0000-0001-5438-284X)
- David Capper (ORCID: https://orcid.org/0000-0003-1945-497X)
- Dorothee Gramatzki (ORCID: https://orcid.org/0000-0002-9054-5498)
- Antje Wick (ORCID: https://orcid.org/0000-0003-0020-6386)
- Simon Paine (ORCID: https://orcid.org/0000-0002-1434-3931)
- Philipp Sievers (ORCID: https://orcid.org/0000-0003-3237-6021)
- Andreas von Deimling (ORCID: https://orcid.org/0000-0002-5863-540X)
- Estelle Healy (ORCID: https://orcid.org/0000-0002-3463-1068)
- Luca Regli (ORCID: https://orcid.org/0000-0003-4639-4474)
- Tibor Hortobágyi (ORCID: https://orcid.org/0000-0001-5732-7942)
- Ute Pohl
- Felix Sahm (ORCID: https://orcid.org/0000-0001-5441-1962)
- Malte Mohme (ORCID: https://orcid.org/0000-0003-0627-9092)
- Stefanie Quach (ORCID: https://orcid.org/0000-0003-2914-3649)
- Jamal K. Benhamida (ORCID: https://orcid.org/0000-0001-5542-9857)
- Ho‐Keung Ng (ORCID: https://orcid.org/0000-0002-2614-2213)
- Ulrich Schüller (ORCID: https://orcid.org/0000-0002-8731-1121)
- Andrea Bink (ORCID: https://orcid.org/0000-0002-2163-3400)
- Julia Onken (ORCID: https://orcid.org/0000-0002-2859-4395)
- Emilie Le Rhun
- Matija Snuderl (ORCID: https://orcid.org/0000-0003-0752-0917)
- Wolfgang Wick (ORCID: https://orcid.org/0000-0002-6171-634X)
- Olaf Ansorge (ORCID: https://orcid.org/0000-0003-1825-5434)
- Tereza Lausova
- Katharina Drueschler
- Evangelia D. Razis (ORCID: https://orcid.org/0000-0003-3873-2947)
- Ghazaleh Tabatabai (ORCID: https://orcid.org/0000-0002-3542-8782)
- David Rieger (ORCID: https://orcid.org/0009-0003-6032-4760)
- Claude Alain Maurage
- Joerg Felsberg
- Leslie Bridges
Institutions
- Entrust (GB)
- Memorial Sloan Kettering Cancer Center (US)
- University College London Hospitals NHS Foundation Trust (GB)
- Universität Hamburg (DE)
- University of Freiburg (DE)
- Chinese University of Hong Kong (HK)
- Heidelberg University (DE)
- Université de Lille (FR)
- Queen Elizabeth Hospital Birmingham (GB)
- St George’s University Hospitals NHS Foundation Trust (GB)
- University Hospital Heidelberg (DE)
- LMU Klinikum (DE)
- NYU Langone Health (US)
- Düsseldorf University Hospital (DE)
- University Hospital of Zurich (CH)
- University Medical Center Hamburg-Eppendorf (DE)
- Hygeia Hospital (GR)
- University Children's Hospital Tübingen (DE)
- Royal Hospital (OM)
- Queen's Medical Centre (GB)
- Frankfurt Cancer Institute (DE)
- Heinrich Heine University Düsseldorf (DE)
- University College London (GB)
- Charité - Universitätsmedizin Berlin (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Neuro-Oncology
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1093/neuonc/noae165.0704
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00