title: Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours.
abstract: OBJECTIVE
  Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs) represent the most common histological entities within the spectrum of glioneuronal tumours (GNTs). The wide variability of morphological features complicates histological classification, including discrimination from prognostically distinct diffuse low-grade astrocytomas (AIIs). This study was performed to increase our understanding of these tumours.
  
  
  METHODS
  We studied chromosomal copy number aberrations (CNAs) by genome-wide sequencing in a large cohort of GNTs and linked these to comprehensive histological analysis and clinical characteristics. One hundred fourteen GNTs were studied: 50 GGs and 64 DNTs. Also, a data set of CNAs from 38 diffuse AIIs was included.
  
  
  RESULTS
  The most frequent CNAs in both GGs and DNTs were gains at chromosomes 5 and 7, often concurrent, and gain at chromosome 6. None of the CNAs was linked to histological subtype, immunohistochemical features or to clinical characteristics. Comparison of AIIs and diffuse GNTs revealed that gain at whole chromosome 5 is only observed in GNTs. CNA patterns indicative of chromothripsis were detected in three GNTs.
  
  
  CONCLUSIONS
  We conclude that GNTs with diverse morphologies share molecular features, and our findings support the need to improve classification and differential diagnosis of tumour entities within the spectrum of GNTs, as well as their distinction from other gliomas.
authors.affiliation: Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Avanita S
authors.initials: AS
authors.lastname: Prabowo
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hinke Foka
authors.initials: HF
authors.lastname: van Thuijl
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Ilari
authors.initials: I
authors.lastname: Scheinin
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daoud
authors.initials: D
authors.lastname: Sie
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hendrik F
authors.initials: HF
authors.lastname: van Essen
authors.affiliation: Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anand M
authors.initials: AM
authors.lastname: Iyer
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wim G M
authors.initials: WG
authors.lastname: Spliet
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.|Clinical Neurophysiology/Rudolf Magnus Institute for Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cyrille H
authors.initials: CH
authors.lastname: Ferrier
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter C
authors.initials: PC
authors.lastname: van Rijen
authors.affiliation: Department of Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Veersema
authors.affiliation: Neuropathology Department, University College London Institute of Neurology, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Thom
authors.affiliation: Department of Paediatric Oncology, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annetteke Y N
authors.initials: AY
authors.lastname: Schouten-van Meeteren
authors.affiliation: Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: Department of (Neuro)Pathology, University of Amsterdam, Amsterdam, The Netherlands.|Swammerdam Institute for Life Sciences, Centre for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.|SEIN - Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D018303:Ganglioglioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D055815:Young Adult
keywords: copy number aberrations; dysembryoplastic neuroepithelial tumour; ganglioglioma; long-term epilepsy-associated tumours; whole genome sequencing