Integrated genomic analyses of de novo pathways underlying atypical meningiomas

Akdes Serin Harmancı, Mark W. Youngblood, Victoria E. Clark, Süleyman Coşkun, Octavian Henegariu, Daniel Duran, E. Zeynep Erson-Omay, Leon D. Kaulen, Tong Ihn Lee, Brian J. Abraham, Matthias Simon, Boris Krischek, Marco Timmer, Roland Goldbrunner, S. Bülent Omay, Jacob Baranoski, Burçin Baran, Geneive Carrión-Grant, Hanwen Bai, Ketu Mishra-Gorur, Johannes Schramm, Jennifer Moliterno, Alexander O. Vortmeyer, Kaya Bilgüvar, Katsuhito Yasuno, Richard A. Young and Murat Günel ()
Additional contact information
Akdes Serin Harmancı: Yale Program in Brain Tumor Research, Yale School of Medicine
Mark W. Youngblood: Yale Program in Brain Tumor Research, Yale School of Medicine
Victoria E. Clark: Yale Program in Brain Tumor Research, Yale School of Medicine
Süleyman Coşkun: Yale Program in Brain Tumor Research, Yale School of Medicine
Octavian Henegariu: Yale Program in Brain Tumor Research, Yale School of Medicine
Daniel Duran: Yale Program in Brain Tumor Research, Yale School of Medicine
E. Zeynep Erson-Omay: Yale Program in Brain Tumor Research, Yale School of Medicine
Leon D. Kaulen: Yale Program in Brain Tumor Research, Yale School of Medicine
Tong Ihn Lee: Whitehead Institute for Biomedical Research
Brian J. Abraham: Whitehead Institute for Biomedical Research
Matthias Simon: University of Bonn Medical School
Boris Krischek: University Hospital of Cologne
Marco Timmer: University Hospital of Cologne
Roland Goldbrunner: University Hospital of Cologne
S. Bülent Omay: Yale Program in Brain Tumor Research, Yale School of Medicine
Jacob Baranoski: Yale Program in Brain Tumor Research, Yale School of Medicine
Burçin Baran: Yale Program in Brain Tumor Research, Yale School of Medicine
Geneive Carrión-Grant: Yale Program in Brain Tumor Research, Yale School of Medicine
Hanwen Bai: Yale Program in Brain Tumor Research, Yale School of Medicine
Ketu Mishra-Gorur: Yale Program in Brain Tumor Research, Yale School of Medicine
Johannes Schramm: University of Bonn Medical School
Jennifer Moliterno: Yale Program in Brain Tumor Research, Yale School of Medicine
Alexander O. Vortmeyer: Yale School of Medicine
Kaya Bilgüvar: Yale Program in Brain Tumor Research, Yale School of Medicine
Katsuhito Yasuno: Yale Program in Brain Tumor Research, Yale School of Medicine
Richard A. Young: Whitehead Institute for Biomedical Research
Murat Günel: Yale Program in Brain Tumor Research, Yale School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14433

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