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

Mihaela Chirica; Philipp Jurmeister; Daniel Teichmann; Arend Koch; Eilís Perez; Simone Schmid; Michèle Simon; Pablo Hernáiz Driever; Carina Bodden; Cornelis M van Tilburg; Emily C Hardin; Cinzia Lavarino; Jürgen Hench; David Scheie; Jane Cryan; Ales Vicha; Francesca R Buttarelli; An Michiels; Christine Haberler; Paulette Barahona; Bastiaan B J Tops; Tom Jacques; Tore Stokland; Olaf Witt; David T W Jones; David Capper

doi:10.1111/nan.13010

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

Mihaela Chirica, Philipp Jurmeister, Daniel Teichmann, Arend Koch, Eilís Perez, Simone Schmid, Michèle Simon, Pablo Hernáiz Driever, Carina Bodden, Cornelis M van Tilburg, Emily C Hardin, Cinzia Lavarino, Jürgen Hench, David Scheie, Jane Cryan, Ales Vicha, Francesca R Buttarelli, An Michiels, Christine Haberler, Paulette BarahonaBastiaan B J Tops, Tom Jacques, Tore Stokland, Olaf Witt, David T W Jones, David Capper^*

^*Corresponding author for this work

Department of Pathology

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.

Original language	English
Article number	e13010
Journal	Neuropathology and Applied Neurobiology
Volume	50
Issue number	5
Pages (from-to)	e13010
ISSN	0305-1846
DOIs	https://doi.org/10.1111/nan.13010
Publication status	Published - Oct 2024

Keywords

Humans
DNA Methylation
Child
Reproducibility of Results
Glioma/genetics
Brain Neoplasms/genetics
Male
Female
Prospective Studies
Child, Preschool

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Chirica, M., Jurmeister, P., Teichmann, D., Koch, A., Perez, E., Schmid, S., Simon, M., Driever, P. H., Bodden, C., van Tilburg, C. M., Hardin, E. C., Lavarino, C., Hench, J., Scheie, D., Cryan, J., Vicha, A., Buttarelli, F. R., Michiels, A., Haberler, C., ... Capper, D. (2024). DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres. Neuropathology and Applied Neurobiology, 50(5), e13010. Article e13010. https://doi.org/10.1111/nan.13010

DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres. / Chirica, Mihaela; Jurmeister, Philipp; Teichmann, Daniel et al.
In: Neuropathology and Applied Neurobiology, Vol. 50, No. 5, e13010, 10.2024, p. e13010.

Research output: Contribution to journal › Journal article › Research › peer-review

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 & Capper, D 2024, 'DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres', Neuropathology and Applied Neurobiology, vol. 50, no. 5, e13010, pp. e13010. https://doi.org/10.1111/nan.13010

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

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 = "Humans, DNA Methylation, Child, Reproducibility of Results, Glioma/genetics, Brain Neoplasms/genetics, Male, Female, Prospective Studies, Child, Preschool",

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note = "{\textcopyright} 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.",

year = "2024",

month = oct,

doi = "10.1111/nan.13010",

language = "English",

volume = "50",

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issn = "0305-1846",

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T1 - DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres

AU - Chirica, Mihaela

AU - Jurmeister, Philipp

AU - Teichmann, Daniel

AU - Koch, Arend

AU - Perez, Eilís

AU - Schmid, Simone

AU - Simon, Michèle

AU - Driever, Pablo Hernáiz

AU - Bodden, Carina

AU - van Tilburg, Cornelis M

AU - Hardin, Emily C

AU - Lavarino, Cinzia

AU - Hench, Jürgen

AU - Scheie, David

AU - Cryan, Jane

AU - Vicha, Ales

AU - Buttarelli, Francesca R

AU - Michiels, An

AU - Haberler, Christine

AU - Barahona, Paulette

AU - Tops, Bastiaan B J

AU - Jacques, Tom

AU - Stokland, Tore

AU - Witt, Olaf

AU - Jones, David T W

AU - Capper, David

PY - 2024/10

Y1 - 2024/10

N2 - 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.

AB - 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.

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KW - Reproducibility of Results

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KW - Brain Neoplasms/genetics

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KW - Female

KW - Prospective Studies

KW - Child, Preschool

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JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

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

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