title: Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age.
abstract: Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.
authors.affiliation: Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Fontebasso
authors.affiliation: Department of Experimental Pathology, Immunology and Microbiology, American University Of Beirut, Beirut, Lebanon.
authors.forename: Margret
authors.initials: M
authors.lastname: Shirinian
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Dong-Anh
authors.initials: DA
authors.lastname: Khuong-Quang
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Bechet
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Tenzin
authors.initials: T
authors.lastname: Gayden
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: De Jay
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Jacob
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Noha
authors.initials: N
authors.lastname: Gerges
authors.affiliation: Division of Theoretical Bioinformatics, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hutter
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Huriye
authors.initials: H
authors.lastname: Şeker-Cin
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Witt
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Brunet
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bourret
authors.affiliation: Department of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Almos
authors.initials: A
authors.lastname: Klekner
authors.affiliation: Department of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Bognár
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Hauser
authors.affiliation: 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Garami
authors.affiliation: Department of Neurosurgery, Montreal Children's Hospital and McGill University Health Centre, Montreal, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Farmer
authors.affiliation: Department of Neurosurgery, Montreal Children's Hospital and McGill University Health Centre, Montreal, Canada.
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Montes
authors.affiliation: Department of Neurosurgery, Montreal Children's Hospital and McGill University Health Centre, Montreal, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Lambert
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Kwan
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.affiliation: Division of Pediatric Hematology-Oncology and The Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.affiliation: Department of Pathology, Montreal Children's Hospital and McGill University Health Centre, Montreal, Canada.
authors.forename: Steffen
authors.initials: S
authors.lastname: Albrecht
authors.affiliation: Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: Faury
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.|Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Jabado
mesh_terms: D000328:Adult; D000367:Age Factors; D000782:Aneuploidy; D001254:Astrocytoma / Q000145:classification* / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D002648:Child; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; MDM2; PLK2; aneuploidy; pilocytic astrocytoma