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.
Highlights
Oligodendroglial tumours (OT) are a heterogeneous group of gliomas
OT can belong to all three molecular subgroups even though pure oligodendroglial differentiation is strongly associated with the 1p/19q co-deletion[1]
MicroRNA sequencing was performed on 177 samples, and most of them were further profiled on single-nucleotide polymorphism (SNP) arrays (n 1⁄4 161) and DNA methylation arrays (n 1⁄4 104) as described in Supplementary Table 1
Summary
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. The OPC-like group is associated with more aggressive clinical and molecular patterns, including MYC activation. Oligodendroglial tumours (OT), that is, gliomas with an oligodendroglial differentiation, account for B20% of adult diffuse gliomas[1] They form a heterogeneous group of gliomas in terms of clinical, histological and molecular profiles[2]. From a molecular point of view, three main subgroups of adults diffuse gliomas can be distinguished on the basis of two biomarkers, the 1p/19q co-deletion and the isocitrate dehydrogenase (IDH) mutation status[3,4]. One group is associated with more aggressive clinical and molecular patterns, including the MYC pathway activation. MicroRNA (miRNA) sequencing was performed on 177 samples, and most of them were further profiled on single-nucleotide polymorphism (SNP) arrays (n 1⁄4 161) and DNA methylation arrays (n 1⁄4 104) as described in Supplementary Table 1
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