Journal Article

DZNE-2026-00179

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

Sill, M. ; Schrimpf, D. ; Patel, A. ; Sturm, D. ; Jäger, N. ; Sievers, P. ; Schweizer, L. ; Banan, R. ; Reuss, D. ; Suwala, A. ; Korshunov, A. ; Stichel, D. ; Wefers, A. K. ; Hau, A.-C. ; Boldt, H. ; Harter, P. N. ; Abdullaev, Z. ; Benhamida, J. ; Teichmann, D. ; Koch, A. ; Hench, J. ; Frank, S. ; Hasselblatt, M. ; Mansouri, S. ; Díaz de Ståhl, T. ; Serrano, J. ; Ecker, J. ; Selt, F. ; Taylor, M. ; Ramaswamy, V. ; Cavalli, F. ; Berghoff, A. S. ; Bison, B. ; Blattner-Johnson, M. ; Buchhalter, I. ; Buslei, R. ; Calaminus, G. ; Dikow, N. ; Dohmen, H. ; Euskirchen, P. ; Fleischhack, G. ; Gajjar, A. ; Gerber, N. U. ; Gessi, M. ; Gielen, G. H. ; Gnekow, A. ; Gottardo, N. G. ; Haberler, C. ; Hamelmann, S. ; Hans, V. ; Hansford, J. R. ; Hartmann, C. ; Heppner, F. L.DZNE* ; Driever, P. H. ; von Hoff, K. ; Thomale, U. W. ; Tippelt, S. ; Frühwald, M. C. ; Kramm, C. M. ; Schüller, U. ; Schittenhelm, J. ; Schuhmann, M. U. ; Stein, M. ; Ketteler, P. ; Ladanyi, M. ; Jabado, N. ; Jones, B. C. ; Jones, C. ; Karajannis, M. A. ; Ketter, R. ; Kohlhof, P. ; Kordes, U. ; Reinhardt, A. ; Kölsche, C. ; Lamszus, K. ; Lichter, P. ; Maas, S. L. N. ; Mawrin, C. ; Milde, T. ; Mittelbronn, M. ; Monoranu, C.-M. ; Mueller, W. ; Mynarek, M. ; Northcott, P. A. ; Pajtler, K. W. ; Paulus, W. ; Perry, A. ; Blümcke, I. ; Plate, K. H. ; Platten, M. ; Preusser, M. ; Pietsch, T.Extern* ; Prinz, M. ; Reifenberger, G. ; Kristensen, B. W. ; Kool, M. ; Hovestadt, V. ; Ellison, D. W. ; Jacques, T. S. ; Varlet, P. ; Etminan, N. ; Acker, T. ; Weller, M. ; White, C. L. ; Witt, O. ; Herold-Mende, C. ; Debus, J. ; Krieg, S. ; Wick, W. ; Snuderl, M. ; Aldape, K. ; Brandner, S. ; Hawkins, C. ; Horbinski, C. ; Thomas, C. ; Wesseling, P. ; von Deimling, A. ; Capper, D. ; Pfister, S. M. ; Jones, D. T. W. ; Sahm, F.

2026
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.ccell.2025.11.002

Abstract: DNA methylation-based classification is now central to contemporary neuro-oncology, as highlighted by the World Health Organization (WHO) classification of central nervous system (CNS) tumors. We present the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.8), trained on 7,495 methylation profiles, which expands recognized entities from 91 classes in version 11 (v11) to 184 subclasses. This expansion is a result of newly identified tumor types discovered through our large online repository and global collaborations, underscoring CNS tumor heterogeneity. The random forest-based classifier achieves 95% subclass-level accuracy, with its well-calibrated probabilistic scores providing a reliable measure of confidence for each classification. Its hierarchical output structure enables interpretation across subclass, class, family, and superfamily levels, thereby supporting clinical decisions at multiple granularities. Comparative analyses demonstrate that v12.8 surpasses previous versions and conventional WHO-based approaches. These advances highlight the improved precision and practical utility of the updated classifier in personalized neuro-oncology.

Keyword(s): CNS tumors ; DNA methylation ; MLOps ; artificial intelligence ; classification ; epigenetics ; machine learning ; molecular diagnostics ; precision medicine ; tumor heterogeneity

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Contributing Institute(s):

1. Neuroimmunology (AG Heppner)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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