Research findings related to UNITE work packages A02/A03/A06/B01/B03/B04/C01/C06/
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. We investigated how PMMRDGs differ from other gliomas with respect to DNA methylation profile, genomic alterations, histopathology, and clinical outcomes. 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. 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
Suwala AK, Friedel D*, Hinz FE, Mahlknecht PD*, Schinkewitsch S*, Rieder M, Fernandez NR, Stengs L, Chang Y, Ringel A, Haag D, Pusch S*, Stichel D, Schrimpf D, Kramm CM, Wesseling P, Schweizer L, Harter P, Hartmann C, Capper D, Snuderl M, Boldt H, Brandner S, Dohmen H, Acker T, Schittenhelm J, Hasselblatt M, Agardy D*, Bunse T*, Bunse L*, Korshunov A, Herold-Mende C*, Etminan N, Wick W*, Platten M*, Das A, Tabori U, Blattner-Johnson M, Sill M, Sturm D, Pfister SM*, Jones DT*, Sahm F*, von Deimling A*, Reuss DE*. 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. Neuro Oncol. 2026 Jun 3:noag132. doi: 10.1093/neuonc/noag132. Epub ahead of print. PMID: 42236272. * UNITE Principal Investigators and Fellows
