DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres
Por:
Chirica M, Jurmeister P, Teichmann D, Koch A, Perez E, Schmid S, Simon M, Driever PH, Bodden C, van Tilburg CM, Hardin EC, Lavarino C, Hench J, Scheie D, Cryan J, Vicha A, Buttarelli FR, Michiels A, Haberler C, Barahona P, Tops BBJ, Jacques T, Stokland T, Witt O, Jones DTW and Capper D
Publicada:
24 sep 2024
Resumen:
AimsDNA 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.MethodsFour 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.ResultsHigh 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.ConclusionOur 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.
We conducted a laboratory comparison trial involving 12 international laboratories to test the technical aspects of DNA methylation data generation and profile interpretation. Participants received a DNA aliquot of four low-grade gliomas and performed the DNA methylation-based classification and result interpretation without knowledge of histology, interpreted the copy number profiles and conducted DNA sequencing of the BRAF hotspot p.V600. Results showed a high technical reproducibility with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. image
Filiaciones:
Chirica M:
Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Jurmeister P:
Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany
Teichmann D:
Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
Koch A:
Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
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
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
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
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
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
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
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
Lavarino C:
Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain
Hench J:
Institute for Medical Genetics and Pathology, Division of Neuropathology, Universitätsspital Basel, Basel, Switzerland
Scheie D:
Department of Pathology, Rigshospitalet, Copenhagen, Denmark
Cryan J:
Department of Neuropathology, Beaumont Hospital, Dublin, Ireland
Vicha A:
Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
Buttarelli FR:
Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy
Michiels A:
Belgian Society for Pediatric Hematology and Oncology (BSPHO), Brussels, Belgium
Department Pediatric Oncology, UZ Leuven, Leuven, Belgium
Haberler C:
Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
Barahona P:
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Kensington, Australia
Tops BBJ:
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Jacques T:
Department of Developmental Biology and Cancer, UCL GOS Institute of Child Health, University College London, London, UK
Stokland T:
Department of Pediatrics, Universitetssykehuset Nord-Norge, Tromso, Norway
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
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
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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