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.

Suwala, Abigail Kora; Boldt, Henning; Korshunov, Andrey; Snuderl, Matija; Brandner, Sebastian; Reuss, David E; Ringel, Amit; Stengs, Lucie; von Deimling, Andreas; Herold-Mende, Christel; Capper, David; Wick, Wolfgang; Chang, Yuan; Pusch, Stefan; Harter, Patrick; Schittenhelm, Jens; Agardy, Dennis Alexander; Pfister, Stefan; Kramm, Christof M; Hinz, Felix; Haag, Daniel; Sill, Martin; Rieder, Mathias; Mahlknecht, Philipp; Acker, Till; Platten, Michael; Wesseling, Pieter; Blattner-Johnson, Mirjam; Schweizer, Leonille; Das, Anirban; Bunse, Lukas; Jones, David; Friedel, Dennis; Dohmen, Hildegard; Hartmann, Christian; Fernandez, Nicholas R; Schinkewitsch, Sophia; Sahm, Felix; Tabori, Uri; Bunse, Theresa; Schrimpf, Daniel; Sturm, Dominik; Stichel, Damian; Etminan, Nima; Hasselblatt, Martin

doi:10.1093/neuonc/noag132

Journal Article

DKFZ-2026-01349

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.

Suwala, A. K. (First author)DKFZ* ; Friedel, D.DKFZ* ; Hinz, F.DKFZ* ; Mahlknecht, P.DKFZ* ; Schinkewitsch, S. ; Rieder, M. ; Fernandez, N. R. ; Stengs, L. ; Chang, Y. ; Ringel, A. ; Haag, D.DKFZ* ; Pusch, S.DKFZ* ; Stichel, D.DKFZ* ; Schrimpf, D.DKFZ* ; Kramm, C. M. ; Wesseling, P. ; Schweizer, L.DKFZ* ; Harter, P.DKFZ* ; Hartmann, C. ; Capper, D.DKFZ* ; Snuderl, M. ; Boldt, H. ; Brandner, S. ; Dohmen, H. ; Acker, T. ; Schittenhelm, J. ; Hasselblatt, M. ; Agardy, D. A.DKFZ* ; Bunse, T.DKFZ* ; Bunse, L.DKFZ* ; Korshunov, A.DKFZ* ; Herold-Mende, C. ; Etminan, N. ; Wick, W.DKFZ* ; Platten, M.DKFZ* ; Das, A. ; Tabori, U. ; Blattner-Johnson, M.DKFZ* ; Sill, M.DKFZ* ; Sturm, D.DKFZ* ; Pfister, S.DKFZ* ; Jones, D.DKFZ* ; Sahm, F.DKFZ* ; von Deimling, A.DKFZ* ; Reuss, D. E. (Last author)DKFZ*

2026
Oxford Univ. Press Oxford

Neuro-Oncology nn, nn (2026) [10.1093/neuonc/noag132]

Abstract: 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.

Keyword(s): MMRD ; Mismatch repair ; long-term survivor ; lynch ; type I interferon