TY  - JOUR
AU  - Chirica, Mihaela
AU  - Jurmeister, Philipp
AU  - Teichmann, Daniel
AU  - Koch, Arend
AU  - Perez, Eilis
AU  - Schmid, Simone
AU  - Simon, Michèle
AU  - Driever, Pablo Hernáiz
AU  - Bodden, Carina
AU  - van Tilburg, Cornelis Martinus
AU  - Hardin, Emily Cecilia
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
TI  - DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres.
JO  - Neuropathology & applied neurobiology
VL  - 50
IS  - 5
SN  - 0305-1846
CY  - Oxford [u.a.]
PB  - Wiley-Blackwell
M1  - DKFZ-2024-02072
SP  - e13010
PY  - 2024
AB  - 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.
KW  - Humans
KW  - DNA Methylation
KW  - Child
KW  - Reproducibility of Results
KW  - Glioma: genetics
KW  - Glioma: diagnosis
KW  - Glioma: pathology
KW  - Brain Neoplasms: genetics
KW  - Brain Neoplasms: diagnosis
KW  - Brain Neoplasms: pathology
KW  - Male
KW  - Female
KW  - Prospective Studies
KW  - Child, Preschool
KW  - CNS tumour (Other)
KW  - DNA methylation (Other)
KW  - interlaboratory comparison trial (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39410806
DO  - DOI:10.1111/nan.13010
UR  - https://inrepo02.dkfz.de/record/294044
ER  -