miRNA data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas. miRNA data for an Integrated genomic analysis of oligodendroglial tumours identifies subgroups of 1p/19q co-deleted oligodendrogliomas

A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Oligodendroglial tumours (OT) are a heterogeneous group of gliomas. Three molecular subgroups are currently distinguished based on the IDH mutation and the 1p/19q co-deletion. Here we performed an integrated analysis of the transcriptome, genome and methylome of 156 OT. Beyond the 3 well-known molecular classes, our multi-omics classification revealed 3 subgroups within 1p/19q co-deleted tumours, associated with different expression patterns of oligodendroglial progenitor cell (OPC), astrocytic, oligodendrocytic and neuronal lineage genes. The validity of these 3 subgroups was confirmed on public datasets. The OPC-like group was associated with a more aggressive histological and genomic profile and with MYC activation that occurred through various alterations including MYC locus genomic gain, MYC exon 3 hypo-methylation and down-regulation of microRNA-34b/c. In the lower grade glioma TCGA dataset, the OPC-like group was associated with a poorer outcome independently from histological grade. Our study unravels previously unrecognized heterogeneity among 1p/19q co-deleted tumours.

法国国家抗癌联盟（Ligue Nationale Contre le Cancer）发起的肿瘤识别卡（Cartes d'Identite des Tumeurs, CIT）项目（项目网址：http://cit.ligue-cancer.net）：少突胶质细胞瘤（Oligodendroglial tumours, OT）是一类异质性胶质瘤。当前基于异柠檬酸脱氢酶（IDH）突变与1p/19q共缺失状态，可将其划分为3个分子亚型。本研究对156例OT的转录组、基因组与甲基化组开展了整合分析。除3种已被广泛认知的分子亚型外，我们通过多组学分类在1p/19q共缺失型肿瘤中进一步区分出3个亚型，这些亚型分别呈现出少突胶质细胞祖细胞（Oligodendroglial progenitor cell, OPC）、星形细胞、少突胶质细胞及神经元谱系基因的差异化表达模式。上述3个亚型的分类有效性已在公共数据集中得到验证。其中类OPC亚型具有更高的侵袭性组织学与基因组特征，且伴随MYC基因激活——该激活可通过多种遗传改变实现，包括MYC位点基因组扩增、MYC外显子3低甲基化，以及微小RNA-34b/c的表达下调。在低级别胶质瘤癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据集中，类OPC亚型与更差的临床预后相关，且该相关性不受组织学分级的影响。本研究揭示了1p/19q共缺失型肿瘤中此前未被认知的异质性。