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

Mihaela Chirica¹, Philipp Jurmeister², Daniel Teichmann¹, Arend Koch¹, Eilís Perez^{1

3

4}, Simone Schmid^{1

3}, Michèle Simon⁵, Pablo Hernáiz Driever⁵, Carina Bodden^{6

7

8}, Cornelis M van Tilburg^{6

7

8

9

10}, Emily C Hardin^{6

7

8

9

10}, Cinzia Lavarino¹¹, Jürgen Hench¹², David Scheie¹³, Jane Cryan¹⁴, Ales Vicha¹⁵, Francesca R Buttarelli¹⁶, An Michiels^{17

18}, Christine Haberler¹⁹, Paulette Barahona²⁰, Bastiaan B J Tops²¹, Tom Jacques²², Tore Stokland²³, Olaf Witt^{6

7

8

9

10}, David T W Jones^{6

9

24}, David Capper^{1

3}

Affiliations

¹ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
³ German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴ Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ 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.
⁶ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
⁷ Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸ German Cancer Consortium (DKTK), Heidelberg, Germany.
⁹ National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
¹⁰ Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
¹¹ Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain.
¹² Institute for Medical Genetics and Pathology, Division of Neuropathology, Universitätsspital Basel, Basel, Switzerland.
¹³ Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
¹⁴ Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
¹⁵ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁶ Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.
¹⁷ Belgian Society for Pediatric Hematology and Oncology (BSPHO), Brussels, Belgium.
¹⁸ Department Pediatric Oncology, UZ Leuven, Leuven, Belgium.
¹⁹ Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
²⁰ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Kensington, Australia.
²¹ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
²² Department of Developmental Biology and Cancer, UCL GOS Institute of Child Health, University College London, London, UK.
²³ Department of Pediatrics, Universitetssykehuset Nord-Norge, Tromso, Norway.
²⁴ Berlin School of Integrative Oncology (BSIO), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

PMID: 39410806
DOI: 10.1111/nan.13010

Comparative Study

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

Mihaela Chirica et al. Neuropathol Appl Neurobiol. 2024 Oct.

. 2024 Oct;50(5):e13010.

doi: 10.1111/nan.13010.

Authors

Affiliations

¹ Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
³ German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴ Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ 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.
⁶ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
⁷ Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁸ German Cancer Consortium (DKTK), Heidelberg, Germany.
⁹ National Center for Tumor Diseases (NCT), Heidelberg, A Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
¹⁰ Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
¹¹ Laboratory of Molecular Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain.
¹² Institute for Medical Genetics and Pathology, Division of Neuropathology, Universitätsspital Basel, Basel, Switzerland.
¹³ Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
¹⁴ Department of Neuropathology, Beaumont Hospital, Dublin, Ireland.
¹⁵ Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁶ Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy.
¹⁷ Belgian Society for Pediatric Hematology and Oncology (BSPHO), Brussels, Belgium.
¹⁸ Department Pediatric Oncology, UZ Leuven, Leuven, Belgium.
¹⁹ Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
²⁰ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Kensington, Australia.
²¹ Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
²² Department of Developmental Biology and Cancer, UCL GOS Institute of Child Health, University College London, London, UK.
²³ Department of Pediatrics, Universitetssykehuset Nord-Norge, Tromso, Norway.
²⁴ Berlin School of Integrative Oncology (BSIO), Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

PMID: 39410806
DOI: 10.1111/nan.13010

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CNS tumour; DNA methylation; interlaboratory comparison trial.

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References

REFERENCES

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

Affiliations

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

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials