Universität zu Köln

Deng, M. Y., Sill, M., Sturm, D., Stichel, D., Witt, H., Ecker, J., Wittmann, A., Schittenhelm, J., Ebinger, M., Schuhmann, M. U., Figarella-Branger, D., Aronica, E., Staszewski, O., Preusser, M., Haberler, C., Lauten, M., Schueller, U., Hartmann, C., Snuderl, M., Dunham, C., Jabado, N., Wesseling, P. ORCID: 0000-0001-5453-5201, Deckert, M., Keyvani, K., Gottardo, N., Giangaspero, F., von Hoff, K., Ellison, D. W., Pietsch, T., Herold-Mende, C., Milde, T., Witt, O., Kool, M., Korshunov, A., Wick, W., von Deimling, A., Pfister, S. M., Jones, D. T. W. and Sahm, F. (2020). Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14. Neuropathol. Appl. Neurobiol., 46 (5). S. 422 - 431. HOBOKEN: WILEY. ISSN 1365-2990

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Deng, M. Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sill, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sturm, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stichel, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Witt, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ecker, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittmann, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schittenhelm, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebinger, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuhmann, M. U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Figarella-Branger, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aronica, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Staszewski, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Preusser, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Haberler, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lauten, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schueller, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Snuderl, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dunham, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jabado, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wesseling, P. UNSPECIFIED orcid.org/0000-0001-5453-5201 UNSPECIFIED Deckert, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Keyvani, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gottardo, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giangaspero, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Hoff, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ellison, D. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pietsch, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herold-Mende, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Milde, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Witt, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kool, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Korshunov, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wick, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Deimling, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, S. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jones, D. T. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahm, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-345419
DOI:	10.1111/nan.12590
Journal or Publication Title:	Neuropathol. Appl. Neurobiol.
Volume:	46
Number:	5
Page Range:	S. 422 - 431
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2990
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METHYLATION-BASED CLASSIFICATION; MEDULLOBLASTOMA; SUBGROUPS; FUSION; SYSTEM Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34541