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An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

ABSTRACT: 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.

SUBMITTER: Collord G

PROVIDER: S-EPMC6131140 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

Collord Grace G Tarpey Patrick P Kurbatova Natalja N Martincorena Inigo I Moran Sebastian S Castro Manuel M Nagy Tibor T Bignell Graham G Maura Francesco F Young Matthew D MD Berna Jorge J Tubio Jose M C JMC McMurran Chris E CE Young Adam M H AMH Sanders Mathijs M Noorani Imran I Price Stephen J SJ Watts Colin C Leipnitz Elke E Kirsch Matthias M Schackert Gabriele G Pearson Danita D Devadass Abel A Ram Zvi Z Collins V Peter VP Allinson Kieren K Jenkinson Michael D MD Zakaria Rasheed R Syed Khaja K Hanemann C Oliver CO Dunn Jemma J McDermott Michael W MW Kirollos Ramez W RW Vassiliou George S GS Esteller Manel M Behjati Sam S Brazma Alvis A Santarius Thomas T McDermott Ultan U

Scientific reports 20180910 1

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/S ...[more]

PMID: 30202034

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Project description:BackgroundGastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction.MethodsThe lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs.ResultsDifferentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells.ConclusionsThe authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

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An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

Publications

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

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