Outcome-associated factors in a molecularly defined cohort of central neurocytoma

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.

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Journal
Acta Neuropathologica
Published
2025-06-11
DOI
https://doi.org/10.1007/s00401-025-02894-3
Citations
1
Primary Topic
Glioma Diagnosis and Treatment
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article
Field-Weighted Citation Impact
1.63

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article

Outcome-associated factors in a molecularly defined cohort of central neurocytoma

Sebastian Brandner, Helena Radbruch, Majid Esmaeilzadeh, Peter Vajkoczy et al.
1 citations
Acta Neuropathologica
Glioma Diagnosis and Treatment
1.63
article

Outcome-associated factors in a molecularly defined cohort of central neurocytoma

Sebastian Brandner, Helena Radbruch, Majid Esmaeilzadeh, Peter Vajkoczy, Carsten Dittmayer, Christian Johannes Hartmann, Abigail K. Suwala, Georgios Ntoulias, Julia E. Neumann, Christian Thomas, Sven-Axel May, Leonille Schweizer, Felix Behling, David Capper, Wolf Mueller, Marcus Czabanka, Peter Kuzman, Andreas von Deimling, Werner Paulus, Oday Atallah, Rudi Beschorner, Daniel Teichmann, Michael Müther, Julia Onken, David Kaul, Werner Stenzel, Teresa G. Krieger, Joachim P. Steinbach, Michael Bockmayr, Katharina Johanna Weber, Frank L. Heppner, Katharina Wenger-Alakmeh, Franziska M. Ippen, Joachim K. Krauss, Arend Koch, Maja Krech, Karl H. Plate, Amos Muench
article en
1 citations

Abstract

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 NeuropathologicaVol. 149(1)
Goethe University Frankfurt (DE), Carl von Ossietzky Universität Oldenburg (DE), Helmholtz Association of German Research Centres (DE), University College London Hospitals NHS Foundation Trust (GB), Universität Hamburg (DE), University of Potsdam (DE), German Cancer Research Center (DE), Heidelberg University (DE), University of Applied Sciences Potsdam (DE), German Center for Neurodegenerative Diseases (DE), University Hospital Heidelberg (DE), Senckenberg Research Institute and Natural History Museum Frankfurt/M (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), ift Rosenheim (DE), University Hospital Münster (DE), University Medical Center Hamburg-Eppendorf (DE), Kinderkrebs-Zentrum Hamburg (DE), University Children's Hospital Tübingen (DE), University Hospital Leipzig (DE), University Hospital Frankfurt (DE), Rosenheim Technical University of Applied Sciences (DE), Frankfurt Cancer Institute (DE), Klinikum Chemnitz (DE), University College London (GB), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE)
Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Krebshilfe, Deutschen Konsortium für Translationale Krebsforschung, Berlin Institute of Health
Good health and well-being
Openalex Percentile: Top 16%
Glioma Diagnosis and Treatment
1.63
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