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
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772610X24000588
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author 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
author_facet 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
author_sort Maria Filippidou
collection DOAJ
description 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.
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spelling doaj-art-ce2d0da5e5cf4084ae1b72f61ef996e22025-08-20T02:50:13ZengElsevierEJC Paediatric Oncology2772-610X2024-12-01410019810.1016/j.ejcped.2024.100198The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in GreeceMaria Filippidou0Stavros Glentis1Ilona Binenbaum2Martin Sill3Kleoniki Roka4Antonia Vlachou5Georgia Avgerinou6Jonas Ecker7Florian Selt8Martin Hasselblatt9Mirjam Blattner-Johnson10Kathrin Schramm11Clio Trougkou12Dimitrios Doganis13Nikolaos Katzilakis14Vita Ridola15Evgenia Papakonstantinou16Vassilios Papadakis17Emmanouel Hatzipantelis18Eleftheria Kokkinou19Roser Pons20Christina Kanaka-Gantenbein21Dominik Sturm22Steffen Hirsch23Nicola Dikow24Kristian W. Pajtler25Cornelis M. van Tilburg26Michael C. Frühwald27Till Milde28Olaf Witt29David T.W. Jones30Andreas Von Deimling31Felix Sahm32Kalliopi Stefanaki33Stefan M. Pfister34Antonis Kattamis35Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, Greece; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Correspondence to: Division of Pediatric Oncology-Hematology, First Department of Pediatrics, National and Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Levadeias 8, Athens 11527, Greece.Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, GermanyInstitute of Neuropathology, University Hospital Münster, Münster, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceOncology Department, P&A Kyriakou Children's Hospital, Athens, GreeceDepartment of Pediatric Hematology-Oncology, University Hospital of Heraklion, School of Medicine, University of Crete, Heraklion, GreeceDepartment of Pediatric Oncology and Hematology, MITERA Children’s Hospital, Athens, GreeceDepartment of Pediatric Hematology and Oncology, Hippokration General Hospital, Thessaloniki, GreeceDepartment of Pediatric Hematology-Oncology (TAO), Aghia Sophia Children’s Hospital, 8 Levadias Street, Athens, GreeceChildren and Adolescent Hematology-Oncology Unit, 2nd Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki AHEPA University Hospital, Thessaloniki, GreeceFirst Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Agia Sophia Children's Hospital, Athens, GreeceFirst Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Agia Sophia Children's Hospital, Athens, GreeceFirst Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Agia Sophia Children's Hospital, Athens, GreeceDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University Hospital, Heidelberg, GermanyHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, GermanySwabian Children's Cancer Center, Pediatrics and Adolescent Medicine, Faculty of Medicine, University Augsburg, Augsburg, GermanyHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; University Hospital Jena, Department of Pediatrics and Adolescent Medicine, Friedrich Schiller University Jena, Jena, Germany; Comprehensive Cancer Center Central Germany (CCCG), Jena, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Im Neuenheimer Feld 280, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, GermanyDepartment of Pathology, ''Aghia Sophia'' Children's Hospital, Athens, GreeceHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumour Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Im Neuenheimer Feld 460, Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg, Germany; National Center for Tumour Diseases (NCT) Heidelberg, Heidelberg, GermanyDivision of Pediatric Hematology-Oncology, First Department of Pediatrics, National &amp; Kapodistrian University of Athens, ''Aghia Sophia'' Children's Hospital, Full Member of ERN PaedCan, Athens, GreeceBackground: 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.http://www.sciencedirect.com/science/article/pii/S2772610X24000588PaediatricsBrain tumoursClassificationDiagnosisDNA methylation
spellingShingle 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
The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
EJC Paediatric Oncology
Paediatrics
Brain tumours
Classification
Diagnosis
DNA methylation
title The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
title_full The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
title_fullStr The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
title_full_unstemmed The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
title_short The impact of methylome analysis on the diagnosis and treatment of CNS tumours in children and adolescents: A population-based study in Greece
title_sort impact of methylome analysis on the diagnosis and treatment of cns tumours in children and adolescents a population based study in greece
topic Paediatrics
Brain tumours
Classification
Diagnosis
DNA methylation
url http://www.sciencedirect.com/science/article/pii/S2772610X24000588
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AT felixsahm impactofmethylomeanalysisonthediagnosisandtreatmentofcnstumoursinchildrenandadolescentsapopulationbasedstudyingreece
AT kalliopistefanaki impactofmethylomeanalysisonthediagnosisandtreatmentofcnstumoursinchildrenandadolescentsapopulationbasedstudyingreece
AT stefanmpfister impactofmethylomeanalysisonthediagnosisandtreatmentofcnstumoursinchildrenandadolescentsapopulationbasedstudyingreece
AT antoniskattamis impactofmethylomeanalysisonthediagnosisandtreatmentofcnstumoursinchildrenandadolescentsapopulationbasedstudyingreece