Integrated multi-omics analysis of oligodendroglial tumours identifies three subgroups of 1p/19q co-deleted gliomas

Aurélie Kamoun, Ahmed Idbaih, Caroline Dehais, Nabila Elarouci, Catherine Carpentier, Eric Letouzé, Carole Colin, Karima Mokhtari, Anne Jouvet, Emmanuelle Uro-Coste, Nadine Martin-Duverneuil, Marc Sanson, Jean-Yves Delattre, Dominique Figarella-Branger, Aurélien de Reyniès () and François Ducray ()
Additional contact information
Aurélie Kamoun: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Ahmed Idbaih: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l’Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975
Caroline Dehais: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin
Nabila Elarouci: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Catherine Carpentier: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l’Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975
Eric Letouzé: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
Carole Colin: Université de la Méditerranée, Aix-Marseille, Faculté de Médecine La Timone, CRO2, UMR 911
Karima Mokhtari: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l’Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975
Anne Jouvet: Hôpital Neurologique, Hospices Civils de Lyon
Emmanuelle Uro-Coste: CHU Toulouse, Hôpital de Rangueil, Service d’Anatomie et Cytologie Pathologique
Nadine Martin-Duverneuil: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neuroradiologie
Marc Sanson: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l’Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975
Jean-Yves Delattre: Université Pierre et Marie Curie Paris 6, Centre de Recherche de l’Institut de Cerveau et de la Moelle Epinière (CRICM), UMR 975
Dominique Figarella-Branger: Université de la Méditerranée, Aix-Marseille, Faculté de Médecine La Timone, CRO2, UMR 911
Aurélien de Reyniès: Programme Cartes d’Identité des Tumeurs (CIT), Ligue Nationale Contre Le Cancer
François Ducray: Hospices Civils de Lyon, Hôpital Neurologique, Service de Neuro-Oncologie

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11263

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