The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece

The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece

Background: The recently published WHO classification of central nervous system (CNS) tumours recognizes DNA methylation profiling as a desirable and, for some diagnoses, essential diagnostic tool adjunctive to conventional histopathology. DNA methylation profiling is not routinely available in many...

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Main Authors: Maria Filippidou, Stavros Glentis, Ilona Binenbaum, Martin Sill, Kleoniki Roka, Antonia Vlachou, Georgia Avgerinou, Jonas Ecker, Florian Selt, Martin Hasselblatt, Mirjam Blattner-Johnson, Kathrin Schramm, Clio Trougkou, Dimitrios Doganis, Nikolaos Katzilakis, Vita Ridola, Evgenia Papakonstantinou, Vassilios Papadakis, Emmanouel Hatzipantelis, Eleftheria Kokkinou, Roser Pons, Christina Kanaka-Gantenbein, Dominik Sturm, Steffen Hirsch, Nicola Dikow, Kristian W. Pajtler, Cornelis M. van Tilburg, Michael C. Frühwald, Till Milde, Olaf Witt, David T.W. Jones, Andreas Von Deimling, Felix Sahm, Kalliopi Stefanaki, Stefan M. Pfister, Antonis Kattamis
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:EJC Paediatric Oncology
Subjects:
Paediatrics
Brain tumours
Classification
Diagnosis
DNA methylation
Online Access:http://www.sciencedirect.com/science/article/pii/S2772610X24000588
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Summary:Background: The recently published WHO classification of central nervous system (CNS) tumours recognizes DNA methylation profiling as a desirable and, for some diagnoses, essential diagnostic tool adjunctive to conventional histopathology. DNA methylation profiling is not routinely available in many countries, including Greece. Methods: In this collaborative study, we report the DNA methylation results in a series of children and adolescents with CNS tumours in Greece (2018–2023). In total, 130 tumour samples were analyzed using the latest applicable version of the Heidelberg brain tumour classifier. Results: Upon initial analysis, 80 % (104/130) achieved calibrated scores (Cs) ≥ 0.9 and matched an established methylation class family/subclass. Among them, methylation results confirmed (90/104, 86.5 %), refined (50/104, 48 %) or changed (10/104, 9.6 %) the histological diagnosis. Only four results were regarded as non-contributing (4/104, 3.9 %). Twenty-six tumour samples received Cs < 0.9. Despite low scores, methylation results supported the initial diagnosis with lower confidence in 38.5 % (10/26) and established the diagnosis in two tumours with non-conclusive histopathology. Additional t-distributed stochastic neighbour embedding (t-SNE) analysis allowed the possible classification of twelve tumours. Nine more samples reached high Cs using the newer brain tumour classifiers, since available. Samples co-tested in Greece demonstrated excellent test reproducibility, supporting the analysis' local implementation. Methylome profiling impacted the clinical management of 40 % of patients, modifying stratification, prognosis, or treatment approach. Conclusions: This study supports the need to integrate methylome analysis into routine diagnostics in our country and highlights the importance of collaboration between European pediatric oncology centres.
ISSN:2772-610X

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