title: Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas.
abstract: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished on the basis of the IDH mutation and 1p/19q co-deletion. Here we present an integrated analysis of the transcriptome, genome and methylome of 156 OT. Not only does our multi-omics classification match the current classification but also reveals three subgroups within 1p/19q co-deleted tumours, associated with specific expression patterns of nervous system cell types: oligodendrocyte, oligodendrocyte precursor cell (OPC) and neuronal lineage. We confirm the validity of these three subgroups using public datasets. Importantly, the OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. We show that the MYC activation occurs through various alterations, including MYC genomic gain, MAX genomic loss, MYC hypomethylation and microRNA-34b/c down-regulation. In the lower grade glioma TCGA dataset, the OPC-like group is associated with a poorer outcome independently of histological grade. Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumours.
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kamoun
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975, 75013 Paris, France.|INSERM U975, 75013 Paris, France.|CNRS, UMR 7225, 75013 Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Nabila
authors.initials: N
authors.lastname: Elarouci
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975, 75013 Paris, France.|INSERM U975, 75013 Paris, France.|CNRS, UMR 7225, 75013 Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Carpentier
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Letouzé
authors.affiliation: Université de la Méditerranée, Aix-Marseille, Faculté de Médecine La Timone, CRO2, UMR 911, 13885 Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Colin
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975, 75013 Paris, France.|INSERM U975, 75013 Paris, France.|CNRS, UMR 7225, 75013 Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Neuropathologie R. Escourolle, 75013 Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: Département de Pathologie et Neuropathologie, Hôpital Neurologique, Hospices Civils de Lyon, 69374 Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jouvet
authors.affiliation: CHU Toulouse, Hôpital de Rangueil, Service d'Anatomie et Cytologie Pathologique, 31400 Toulouse, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Uro-Coste
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neuroradiologie, 75013 Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin-Duverneuil
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975, 75013 Paris, France.|INSERM U975, 75013 Paris, France.|CNRS, UMR 7225, 75013 Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, 75013 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l'Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975, 75013 Paris, France.|INSERM U975, 75013 Paris, France.|CNRS, UMR 7225, 75013 Paris, France.|AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, 75013 Paris, France.|Onconeurotek, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: Université de la Méditerranée, Aix-Marseille, Faculté de Médecine La Timone, CRO2, UMR 911, 13885 Marseille, France.|AP-HM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, 13885 Marseille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.affiliation: Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, 75013 Paris, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.affiliation: Hospices Civils de Lyon, Hôpital Neurologique, Service de Neuro-Oncologie, 69374 Lyon, France.|Department of Cancer Cell Plasticity, Cancer Research Centre of Lyon, INSERM U1052, CNRS UMR5286, 69008 Lyon, France.|Université Claude Bernard Lyon 1, 69000 Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ducray
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D016000:Cluster Analysis; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics; D005910:Glioma / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D009837:Oligodendroglioma / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D016019:Survival Analysis; D059467:Transcriptome; D055815:Young Adult
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc