Integrated genomic analyses of de novo pathways underlying atypical meningiomas

Akdes Serin Harmancl, Mark W. Youngblood, Victoria E. Clark, Süleyman CoÅ Kun, 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-GorurJohannes Schramm, Jennifer Moliterno, Alexander O. Vortmeyer, Kaya Bilgüvar, Katsuhito Yasuno, Richard A. Young, Murat Günel

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Article number14433
JournalNature communications
Volume8
DOIs
StatePublished - Feb 14 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Integrated genomic analyses of de novo pathways underlying atypical meningiomas'. Together they form a unique fingerprint.

  • Cite this

    Harmancl, A. S., Youngblood, M. W., Clark, V. E., CoÅ Kun, S., Henegariu, O., Duran, D., Erson-Omay, E. Z., Kaulen, L. D., Lee, T. I., Abraham, B. J., Simon, M., Krischek, B., Timmer, M., Goldbrunner, R., Omay, S. B., Baranoski, J., Baran, B., Carrión-Grant, G., Bai, H., ... Günel, M. (2017). Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nature communications, 8, [14433]. https://doi.org/10.1038/ncomms14433