Path-05. Clinical, Pathological and Molecular Disease Characteristics of Diffuse Hemispheric Glioma, H3 G34-mutant
Year: 2024
Type: conference-abstract
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.
Source: Neuro-Oncology
Authors: Emilie Le Rhun, Andrea Bink, Joerg Felsberg, Dorothee Gramatzki, Sebastian Brandner, Jamal K Benhamida, Antje Wick, Joerg C Tonn, Malte Mohme, Ghazaleh Tabatabai, David Capper, Matija Snuderl, Evangelia Razis, Michael Ronellenfitsch, Nicolas Neidert, Ho-Keung Ng, Ute Pohl, Tejus Bale, Stefanie Quach, David Rieger, Ulrich Schüller, Julia Onken, Katharina Drueschler, Claude Alain Maurage, Luca Regli, Estelle Healy, Maya Graham, Tibor Hortobagyi, Simon Paine, Olaf Ansorge, Leslie Bridges, Tereza Lausova, Valentina Medici, Philipp Sievers, Daniel Schrimpf, Wolfgang Wick, Felix Sahm, Guido Reifenberger, Andreas von Deimling, Michael Weller
Institutions: University Hospital Zurich, Düsseldorf University Hospital, University College London Hospitals NHS Foundation Trust, University College London, Memorial Sloan Kettering Cancer Center, University Hospital Heidelberg, Ludwig-Maximilians-Universität München, University Medical Center Hamburg-Eppendorf, Universitätsklinikum Tübingen, Charité - Universitätsmedizin Berlin, NYU Langone Health, Hygeia Hospital, Frankfurt Cancer Institute, University of Freiburg, Chinese University of Hong Kong, Queen Elizabeth Hospital Birmingham, Centre Hospitalier Universitaire de Lille, Royal Victoria Hospital, Queen's Medical Centre, St George’s University Hospitals NHS Foundation Trust
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404237374