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Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Aims DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing...

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Main Authors: Deng, Maximilian (Author) , Sill, Martin (Author) , Sturm, Dominik (Author) , Stichel, Damian (Author) , Witt, Hendrik (Author) , Ecker, Jonas (Author) , Wittmann, A. (Author) , Schittenhelm, J. (Author) , Ebinger, M. (Author) , Schuhmann, M. U. (Author) , Figarella‐Branger, D. (Author) , Aronica, E. (Author) , Staszewski, O. (Author) , Preusser, Matthias (Author) , Haberler, C. (Author) , Lauten, M. (Author) , Schüller, U. (Author) , Hartmann, C. (Author) , Snuderl, M. (Author) , Dunham, C. (Author) , Jabado, N. (Author) , Wesseling, P. (Author) , Deckert, M. (Author) , Keyvani, K. (Author) , Gottardo, N. (Author) , Giangaspero, F. (Author) , Hoff, K. von (Author) , Ellison, D. W. (Author) , Pietsch, T. (Author) , Herold-Mende, Christel (Author) , Milde, Till (Author) , Witt, Olaf (Author) , Kool, Marcel (Author) , Korshunov, Andrey (Author) , Wick, Wolfgang (Author) , Deimling, Andreas von (Author) , Pfister, Stefan (Author) , Jones, David T. W. (Author) , Sahm, Felix (Author)
Format: Article (Journal)
Language:English
Published: 2020
In: Neuropathology & applied neurobiology
Year: 2020, Volume: 46, Issue: 5, Pages: 422-430
ISSN:1365-2990
DOI:10.1111/nan.12590
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/nan.12590
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12590
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Author Notes:M.Y. Deng, M. Sill, D. Sturm, D. Stichel, H. Witt, J. Ecker, A. Wittmann, J. Schittenhelm, M. Ebinger, M.U. Schuhmann, D. Figarella‐Branger, E. Aronica, O. Staszewski, M. Preusser, C. Haberler, M. Lauten, U. Schüller, C. Hartmann, M. Snuderl, C. Dunham, N. Jabado, P. Wesseling, M. Deckert, K. Keyvani, N. Gottardo, F. Giangaspero, K. von Hoff, D.W. Ellison, T. Pietsch, C. Herold-Mende, T. Milde, O. Witt, M. Kool, A. Korshunov, W. Wick, A. von Deimling, S.M. Pfister, D.T.W. Jones, F. Sahm

MARC

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520 |a Aims DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the ‘conumee’ package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters. 
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