The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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.
Source: EJC Paediatric Oncology
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
Institutions: German Cancer Research Center, National and Kapodistrian University of Athens, Hopp Children's Cancer Center Heidelberg, Children's Hospital Agia Sophia, ERN PaedCan, Deutsches Konsortium für Translationale Krebsforschung, University Hospital Heidelberg, National Center for Tumor Diseases, University Hospital Münster, Panagiotis & Aglaia Kyriakou Children's Hospital, University of Crete, University Hospital of Heraklion, Ippokrateio General Hospital of Thessaloniki, Aristotle University of Thessaloniki, AHEPA University Hospital, Heidelberg University, University of Augsburg, Jena University Hospital, Friedrich Schiller University Jena
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Award: G1829383154
OpenAlex ID: W4403159160