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

<h2>Abstract</h2><h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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.

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Publication Details

Journal
EJC Paediatric Oncology
Published
2024-10-06
DOI
https://doi.org/10.1016/j.ejcped.2024.100198
Citations
2
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.88

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article

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

Kleoniki Roka, Kristian W. Pajtler, R. Pons, Georgia Avgerinou et al.
2 citations
EJC Paediatric Oncology
Glioma Diagnosis and Treatment
0.88
article

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

Kleoniki Roka, Kristian W. Pajtler, R. Pons, Georgia Avgerinou, Vassilios Papadakis, Dominik Sturm, Εvgenia Papakonstantinou, Steffen Hirsch, Vita Ridola, Jonas Ecker, Martin Hasselblatt, Maria Filippidou, Nicola Dikow, Till Milde, Antonia Vlachou, Stefan M. Pfister, Michael C. Frühwald, Stavros Glentis, Andreas von Deimling, Antonis Kattamis, Nikolaos Katzilakis, Felix Sahm, Christina Kanaka‐Gantenbein, Cornelis Martinus van Tilburg, Ilona Binenbaum, Mirjam Blattner-Johnson, Florian Selt, Eleftheria Kokkinou, Dimitrios Doganis, Martin Sill, Emmanouel Hatzipantelis, David Jones, Clio Trougkou, Kalliopi Stefanaki, Kathrin Schramm, Olaf Witt
article en
2 citations

Abstract

<h2>Abstract</h2><h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusions</h3> 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.

EJC Paediatric OncologyVol. 4
University of Augsburg (DE), German Cancer Research Center (DE), National and Kapodistrian University of Athens (GR), Heidelberg University (DE), AHEPA University Hospital (GR), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), Comprehensive Cancer Center Mainfranken (DE), University Hospital Münster (DE), National Center for Tumor Diseases (DE), Hopp Children's Cancer Center Heidelberg (DE), Children's Hospital Agia Sophia (GR), Mitera Hospital (GR), University Hospital of Heraklion (GR), Panagiotis & Aglaia Kyriakou Children's Hospital (GR), Hippocration General Hospital (GR), Deutsches Konsortium für Translationale Krebsforschung (DE), Friedrich Schiller University Jena (DE)
Helmholtz-Gemeinschaft, National and Kapodistrian University of Athens, Helmholtz Association
Good health and well-being
Openalex Percentile: Top 24%
Glioma Diagnosis and Treatment
0.88
DOIOpen Access PDFOpenAlex
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