An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures
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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
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Collord, G., Tarpey, P., Kurbatova, N. et al. An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures. Sci Rep 8, 13537 (2018). https://doi.org/10.1038/s41598-018-31659-0
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https://doi.org/10.1038/s41598-018-31659-0Sponsors
This work was supported by the Wellcome Trust, Cancer Research UK, Meningioma UK and Tadhg and Marie-Louise Flood. U.M. was personally supported by a Cancer Research UK Clinician Scientist Fellowship; G.C. by a Wellcome Trust Clinical PhD Fellowship (WT098051); F.M. by A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS) and by S.I.E.S. (Società Italiana di Ematologia Sperimentale); S.B. was funded by a Wellcome Trust Intermediate Clinical Research Fellowship and a St. Baldrick’s Foundation Robert J. Arceci Innovation Award. J.M.C.T. is supported by ERC Starting Grant StG-2016_716290_SCUBA CANCERS and by MINECO Grants RYC 2014 14999 and SAF2015-66368-P. J.B. was funded by the charity Brain Tumour Research
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© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/