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Advancing CNS tumor diagnostics with expanded DNA methylation-based classification

Title: Advancing CNS tumor diagnostics with expanded DNA methylation-based classification
Authors: Sill,Martin; Schrimpf,Daniel; Patel,Areeba; Sturm,Dominik; Jäger,Natalie; Sievers,Philipp; Schweizer,Leonille; Banan,Rouzbeh; Reuss,David; Suwala,Abigail; Korshunov,Andrey; Stichel,Damian; Wefers,Annika K; Hau,Ann-Christin; Boldt,Henning; Harter,Patrick N; Abdullaev,Zied; Benhamida,Jamal; Teichmann,Daniel; Koch,Arend; Hench,Jürgen; Frank,Stephan; Hasselblatt,Martin; Mansouri,Sheila; Díaz de Ståhl,Theresita; Serrano,Jonathan; Ecker,Jonas; Selt,Florian; Taylor,Michael; Ramaswamy,Vijay; Cavalli,Florence; Berghoff,Anna S; Bison,Brigitte; Blattner-Johnson,Mirjam; Buchhalter,Ivo; Buslei,Rolf; Calaminus,Gabriele; Dikow,Nicola; Dohmen,Hildegard; Euskirchen,Philipp; Fleischhack,Gudrun; Gajjar,Amar; Gerber,Nicolas U; Gessi,Marco; Gielen,Gerrit H; Gnekow,Astrid; Gottardo,Nicholas G; Haberler,Christine; Hamelmann,Stefan; Hans,Volkmar; Hansford,Jordan R; Hartmann,Christian; Heppner,Frank L; Driever,Pablo Hernaiz; von Hoff,Katja; Thomale,Ulrich W; Tippelt,Stephan; Frühwald,Michael C; Kramm,Christof M; Schüller,Ulrich; Schittenhelm,Jens; Schuhmann,Martin U; Stein,Marco; Ketteler,Petra; Ladanyi,Marc; Jabado,Nada; Jones,Barbara C; Jones,Chris; Karajannis,Matthias A; Ketter,Ralf; Kohlhof,Patricia; Kordes,Uwe; Reinhardt,Annekathrin; Kölsche,Christian; Lamszus,Katrin; Lichter,Peter; Maas,Sybren L N; Mawrin,Christian; Milde,Till; Mittelbronn,Michel; Monoranu,Camelia-Maria; Mueller,Wolf; Mynarek,Martin; Northcott,Paul A; Pajtler,Kristian W; Paulus,Werner; Perry,Arie; Blümcke,Ingmar; Plate,Karl H; Platten,Michael; Preusser,Matthias; Pietsch,Torsten; Prinz,Marco; Reifenberger,Guido; Kristensen,Bjarne W; Kool, Marcel; Hovestadt,Volker; Ellison,David W; Jacques,Thomas S; Varlet,Pascale; Etminan,Nima; Acker,Till; Weller,Michael; White,Christine L; Witt,Olaf; Herold-Mende,Christel; Debus,Jürgen; Krieg,Sandro; Wick,Wolfgang; Snuderl,Matija; Aldape,Ken; Brandner,Sebastian; Hawkins,Cynthia; Horbinski,Craig; Thomas,Christian; Wesseling,Pieter; von Deimling,Andreas; Capper,David; Pfister,Stefan M; Jones,David T W; Sahm,Felix; Neurochirurgie; Brain
Publication Year: 2026
Subject Terms: Journal Article
Description: 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 1535-6108
Relation: https://dspace.library.uu.nl/handle/1874/469014
Availability: https://dspace.library.uu.nl/handle/1874/469014
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.D5772310
Database: BASE