Integrated genomic analyses of de novo pathways underlying atypical meningiomas
Author(s)Youngblood, Mark W.; Clark, Victoria E.; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Baranoski, Jacob; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilg?var, Kaya; Yasuno, Katsuhito; G?nel, Murat; Harmanci, Akdes Serin; Suleyman, Coskun; Omay, S. Bulent; Baran, Burcin; Carrion-Grant, Geneive; Bilguvar, Kaya; Lee, Tong Ihn; Abraham, Brian Joseph; Young, Richard A; ... Show more Show less
MetadataShow full item record
Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Nature Publishing Group
Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep et al. “Integrated Genomic Analyses of de Novo Pathways Underlying Atypical Meningiomas.” Nature Communications 8 (February 2017): 14433 © 2017 The Authors
Final published version