Cancer cell · 2025

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

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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

Аннотация

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.

Предметные рубрики MeSH

Humans DNA Methylation Central Nervous System Neoplasms Biomarkers, Tumor

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

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Аннотация

Предметные рубрики MeSH