Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
Department of Paediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Sci Rep. 2018 Sep 10;8(1):13537. doi: 10.1038/s41598-018-31659-0.
Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance.
间变性脑膜瘤是一种罕见且侵袭性的脑肿瘤，其特征为难治性复发和预后不良。在此，我们对原发性和复发性间变性脑膜瘤的全基因组、转录组和甲基化谱进行了综合分析。一个关键发现是描绘了截然不同的分子亚群，这些亚群与截然相反的生存结果相关。与低级别脑膜瘤相比，间变性肿瘤中存在 SWI/SNF 复合物基因的频繁驱动突变，这些突变仅限于预后不良的亚组。侵袭性疾病的特征还包括 PRC2 活性、干性和上皮-间充质转化增加的转录证据。我们的分析区分了具有预后和治疗意义的生物学上不同的间变性脑膜瘤变体。
