von Maja Krech ; Amos Muench ; Daniel Teichmann ; Peter Kuzman ; Abigail Kora Suwala ; Franziska M. Ippen ; Michael Müther ; Katharina J. Weber ; Katharina Wenger-Alakmeh ; Julia Onken ; Peter Vajkoczy ; Felix Behling ; Sven-Axel May ; Georgios Ntoulias ; Joachim K. Krauss ; Oday Atallah ; Majid Esmaeilzadeh ; Wolf C. Mueller ; Frank L. Heppner ; Helena Radbruch ; Carsten Dittmayer ; Werner Stenzel ; Arend Koch ; David Capper ; David Kaul ; Werner Paulus ; Karl Plate ; Joachim P. Steinbach ; Markus Czabanka ; Rudi Beschorner ; Andreas von Deimling ; Michael Bockmayr ; Julia E. Neumann ; Sebastian Brandner ; Teresa Krieger ; Christian Hartmann ; Christian Thomas ; Leonille Schweizer
Veröffentlicht: 11. Juni 2025 ; Gesehen am 29.10.2025
DNA methylation profiling; FGFR3; Neurocytoma; Progression-free survival; Radiotherapy
Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using atypical features and an elevated Ki67 proliferation index. However, these markers lack consistent definitions, raising the need for objective criteria. Genome-wide DNA methylation profiles were examined in 136 tumors histologically classified as CN. Clinical/histopathological characteristics were assessed in 93/90 cases, and whole-exome sequencing was conducted in 12 cases. Clinical and molecular characteristics were integrated into a survival model to predict progression-free survival (PFS). A diagnosis of CN was epigenetically confirmed in 125 of 136 cases (92%). No DNA methylation subgroups were identified, but global DNA hypomethylation emerged as a hallmark feature of CN associated with higher recurrence risk. Risk stratification based on histological features of atypia and Ki67 proliferation index was not reproducible across neuropathologists. Hypomethylation at the FGFR3 locus, accompanied by increased FGFR3 protein expression, was observed in 97% of cases. Gross total resection was associated with significantly improved PFS compared to STR, while patients undergoing STR receiving radiotherapy had a better outcome (p = 0.0001). Younger patients were identified as having a higher risk of recurrence (p = 0.026). Patient age and treatment strategy were key factors associated with survival outcomes in this cohort. These findings underscore the importance of closer follow-up for younger patients and radiotherapy for STR cases. Furthermore, FGFR3 represents a hallmark feature and potential therapeutic target, warranting further investigation.
Acta neuropathologica Berlin : Springer, 1961 149(2025), Artikel-ID 61, Seite 1-16 Online-Ressource
von Julia Beckhaus ; Svenja Boekhoff ; Katrin Scheinemann ; Freimut H. Schilling ; Gudrun Fleischhack ; Gerhard Binder ; Brigitte Bison ; Torsten Pietsch ; Carsten Friedrich ; Hermann L. Müller
von Jutta Keller ; Thilo Wedel ; Holger Seidl ; Martin Ernst Kreis ; Ivo Raymond van der Voort ; Maximilian Gebhard ; Jost Langhorst ; Petra Lynen ; Oliver Schwandner ; Martin Storr ; Pia van Leeuwen ; Viola Andresen ; Jan Preiß ; Peter Layer ; Hans-Dieter Allescher ; Tilo Andus ; Stephan C. Bischoff ; Stephan Buderus ; M. Claßen ; U. Ehlert ; S. Elsenbruch ; M. Engel ; Axel Enninger ; Wolfgang Fischbach ; Michael H. Freitag ; Thomas Frieling ; Anton Gillessen ; M. Goebel-Stengel ; Juliane Dorothee Gschoßmann ; Felix Gundling ; S. Haag ; W. Häuser ; Ulf Helwig ; Stephan Hollerbach ; G. Holtmann ; M. Karaus ; M. Katschinski ; H. Krammer ; Wolfgang Kruis ; R. Kuhlbusch-Zicklam ; Ahmed Madisch ; H. Matthes ; Stephan Miehlke ; Hubert Mönnikes ; Stefan Müller-Lissner ; B. Niesler ; C. Pehl ; D. Pohl ; Carsten Posovszky ; M. Raithel ; Gabriele Röhrig-Herzog ; R. Schäfert ; M. Schemann ; Anjona Schmidt-Choudhury ; S. Schmiedel ; Anna Schweinlin ; Ilja Juliane Dorothee Schwille-Kiuntke ; A. Stengel ; Jonas Tesarz ; W. Voderholzer ; G. von Boyen ; J. von Schönfeld
von Dennis Plenker ; Miriam Bertrand ; Adrianus J. de Langen ; Richard Riedel ; Carina Lorenz ; Andreas Scheel ; Judith Müller ; Johannes Brägelmann ; Juliane Daßler-Plenker ; Carsten Andreas Kobe ; Thorsten Persigehl ; Alexander Kluge ; Thomas Wurdinger ; Pepijn Schellen ; Gunther Hartmann ; Tobias Zacherle ; Roopika Menon ; Erik Thunnissen ; Reinhard Büttner ; Frank Griesinger ; Jürgen Wolf ; Lukas Heukamp ; Martin Lukas Sos ; Johannes M. Heuckmann
