DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres.


Journal

Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829

Informations de publication

Date de publication:
Oct 2024
Historique:
revised: 02 09 2024
received: 06 05 2024
accepted: 14 09 2024
medline: 16 10 2024
pubmed: 16 10 2024
entrez: 16 10 2024
Statut: ppublish

Résumé

DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions. Four representative low-grade gliomas of distinct histologies were centrally selected, and DNA extraction was performed. Participating laboratories received a DNA aliquot and performed the DNA methylation-based classification and result interpretation without knowledge of tumour histology. Additionally, participants were required to interpret the copy number profile derived from DNA methylation data and conduct DNA sequencing of the BRAF hotspot p.V600 due to its relevance for low-grade gliomas. Results had to be returned within 30 days. High technical reproducibility was observed, with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. DNA methylation-based tumour classification and copy number profile interpretation were consistent across all centres, and BRAF mutation status was accurately reported for all cases. Eleven out of 12 centres successfully reported their analysis within the 30-day timeframe. Our study demonstrates remarkable concordance in DNA methylation profiling and profile interpretation across 12 international centres. These findings underscore the potential contribution of DNA methylation analysis to the harmonisation of brain tumour diagnostics.

Identifiants

pubmed: 39410806
doi: 10.1111/nan.13010
doi:

Types de publication

Journal Article Multicenter Study Comparative Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13010

Subventions

Organisme : The Everest Centre for Research into Paediatric Low-Grade Brain Tumours
ID : GN-000707
Organisme : PLGA Fund at the Paediatric Brain Tumor Foundation
Organisme : University Hospital Motel in Prague, Czech Republic
ID : MH CZ-DRO 00064203
Organisme : World Health Organisation
Organisme : Brain Tumour Charity

Informations de copyright

© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Références

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Auteurs

Mihaela Chirica (M)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Philipp Jurmeister (P)

Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.

Daniel Teichmann (D)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Arend Koch (A)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Eilís Perez (E)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Simone Schmid (S)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Michèle Simon (M)

Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, German HIT-LOGGIC-Registry for pLGG in Children and Adolescents, Berlin, Germany.

Pablo Hernáiz Driever (PH)

Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, German HIT-LOGGIC-Registry for pLGG in Children and Adolescents, Berlin, Germany.

Carina Bodden (C)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.

Cornelis M van Tilburg (CM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Emily C Hardin (EC)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Cinzia Lavarino (C)

Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain.

Jürgen Hench (J)

Institute for Medical Genetics and Pathology, Division of Neuropathology, Universitätsspital Basel, Basel, Switzerland.

David Scheie (D)

Department of Pathology, Rigshospitalet, Copenhagen, Denmark.

Jane Cryan (J)

Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.

Ales Vicha (A)

Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.

Francesca R Buttarelli (FR)

Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.

An Michiels (A)

Belgian Society for Pediatric Hematology and Oncology (BSPHO), Brussels, Belgium.
Department Pediatric Oncology, UZ Leuven, Leuven, Belgium.

Christine Haberler (C)

Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.

Paulette Barahona (P)

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Kensington, Australia.

Bastiaan B J Tops (BBJ)

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.

Tom Jacques (T)

Department of Developmental Biology and Cancer, UCL GOS Institute of Child Health, University College London, London, UK.

Tore Stokland (T)

Department of Pediatrics, Universitetssykehuset Nord-Norge, Tromso, Norway.

Olaf Witt (O)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
Berlin School of Integrative Oncology (BSIO), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

David Capper (D)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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