TY - JOUR
T1 - Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) – a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14
AU - Deng, M. Y.
AU - Sill, M.
AU - Sturm, D.
AU - Stichel, D.
AU - Witt, H.
AU - Ecker, J.
AU - Wittmann, A.
AU - Schittenhelm, J.
AU - Ebinger, M.
AU - Schuhmann, M. U.
AU - Figarella-Branger, D.
AU - Aronica, E.
AU - Staszewski, O.
AU - Preusser, M.
AU - Haberler, C.
AU - Lauten, M.
AU - Schüller, U.
AU - Hartmann, C.
AU - Snuderl, M.
AU - Dunham, C.
AU - Jabado, N.
AU - Wesseling, P.
AU - Deckert, M.
AU - Keyvani, K.
AU - Gottardo, N.
AU - Giangaspero, F.
AU - von Hoff, K.
AU - Ellison, D. W.
AU - Pietsch, T.
AU - Herold-Mende, C.
AU - Milde, T.
AU - Witt, O.
AU - Kool, M.
AU - Korshunov, A.
AU - Wick, W.
AU - von Deimling, A.
AU - Pfister, S. M.
AU - Jones, D. T.W.
AU - Sahm, F.
N1 - Funding Information:
This work was supported by the Everest Centre for Low‐grade Paediatric Brain Tumours (The Brain Tumour Charity, UK), the Paediatric Low‐Grade Astrocytoma Fund (PLGA Fund) at the Paediatric Brain Tumour Foundation (PBTF), the German Cancer Consortium (DKTK), and fellowships from the Mildred‐Scheel doctoral program of the German Cancer Aid and the German National Academic Foundation to M.Y.D (grant number 70112667), the Else Kröner Excellence Program of the Else Kröner‐Fresenius Stiftung (EKFS) to F.S., the Stichting Kinderen Kankervrij (KIKA) to E.A. The study was in part supported by grants from the Friedeberg Charitable Foundation and the Sohn Conference Foundation (M.S.).
Publisher Copyright:
© 2019 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079038769&partnerID=8YFLogxK
U2 - 10.1111/nan.12590
DO - 10.1111/nan.12590
M3 - Journal articles
C2 - 31867747
AN - SCOPUS:85079038769
SN - 0305-1846
VL - 46
SP - 422
EP - 430
JO - Neuropathology and Applied Neurobiology
JF - Neuropathology and Applied Neurobiology
IS - 5
ER -
