Primary Mismatch Repair Deficient Glioma (PMMRDG), IDH-wildtype and H3-wildtype: A Giant Cell Tumor with Potential for Long-Term Survival Occurring at all Ages

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ID: 316060
2026
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Abstract
BACKGROUND: Replication-repair-deficiency is associated with increased risk of developing malignant gliomas. The aim of this study was to investigate primary mismatch repair deficient gliomas (PMMRDGs), a group of IDH-wildtype and H3-wildtype gliomas that is enriched among patients with CMMRD and Lynch syndrome. METHODS: We investigated how PMMRDGs differ from other gliomas with respect to DNA methylation profile, genomic alterations, histopathology, and clinical outcomes. RESULTS: PMMRDGs occur in pediatric, adolescents and the elderly, falling in two related methylation clusters and are characterized by a high frequency of replication repair deficiency. Histology showed multinucleated giant cells, and immunohistochemistry demonstrated loss of MMR protein expression. Survival analysis revealed long-term survival in patients with high mutational burden (>50 mut/Mb) and an intact chromosome 9p region, which was validated in an independent reference cohort. CONCLUSIONS: Overall, our findings indicate that PMMRDGs represent a distinct type of IDH-wildtype gliomas with potential for long-term survival likely driven by immune activation.
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openalex_W7163546131 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Abigail K Suwala, Dennis Friedel, Felix Hinz, Philipp D Mahlknecht, Sophia Schinkewitsch, Mathias Rieder, Nicholas R Fernandez, Lucie Stengs, Yuan Chang, Amit Ringel, Daniel Haag, Stefan Pusch, Damian Stichel, Daniel Schrimpf, Christof M. Kramm, Pieter Wesseling, Leonille Schweizer, Patrick Harter, Christian Hartmann, David Capper, Matija Snuderl, Henning Boldt, Sebastian Brandner, Hildegard Dohmen, Till Acker, Jens Schittenhelm, Martin Hasselblatt, Dennis Agardy, Theresa Bunse, Lukas Bunse, Andrey Korshunov, Christel Herold-Mende, N Etminan, Wolfgang Wick, Michael Platten, Anirban Das, Uri Tabori, Mirjam Blattner-Johnson, Martin Sill, Dominik Sturm, S M Pfister, David TW Jones, Felix Sahm, Andreas von Deimling, David Reuß
Journal journal of neuro-oncology
Year 2026
DOI
10.1093/neuonc/noag132
URL
https://doi.org/10.1093/neuonc/noag132
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