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 Vortmeyer, Kaya Bilgüvar, Katsuhito Yasuno, Richard A. Young, Murat Günel

Research output: Contribution to journalArticle

34 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Polycomb Repressive Complex 2
Meningioma
Tumors
tumors
harbors
mutations
Ports and harbors
phenotype
stem cells
Stem cells
brain
Brain
Binding Sites
Mutation
Gene Regulatory Networks
Genomic Instability
Epigenomics
Brain Neoplasms
Catalytic Domain
Neoplasms

ASJC Scopus subject areas

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

Cite this

Harmancl, A. S., Youngblood, M. W., Clark, V. E., CoÅ Kun, S., Henegariu, O., Duran, D., ... Günel, M. (2017). Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nature communications, 8, [14433]. https://doi.org/10.1038/ncomms14433

Integrated genomic analyses of de novo pathways underlying atypical meningiomas. / Harmancl, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; CoÅ Kun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat.

In: Nature communications, Vol. 8, 14433, 14.02.2017.

Research output: Contribution to journalArticle

Harmancl, AS, Youngblood, MW, Clark, VE, CoÅ Kun, S, Henegariu, O, Duran, D, Erson-Omay, EZ, Kaulen, LD, Lee, TI, Abraham, BJ, Simon, M, Krischek, B, Timmer, M, Goldbrunner, R, Omay, SB, Baranoski, J, Baran, B, Carrión-Grant, G, Bai, H, Mishra-Gorur, K, Schramm, J, Moliterno, J, Vortmeyer, A, Bilgüvar, K, Yasuno, K, Young, RA & Günel, M 2017, 'Integrated genomic analyses of de novo pathways underlying atypical meningiomas', Nature communications, vol. 8, 14433. https://doi.org/10.1038/ncomms14433
Harmancl AS, Youngblood MW, Clark VE, CoÅ Kun S, Henegariu O, Duran D et al. Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nature communications. 2017 Feb 14;8. 14433. https://doi.org/10.1038/ncomms14433
Harmancl, Akdes Serin ; Youngblood, Mark W. ; Clark, Victoria E. ; CoÅ Kun, Süleyman ; Henegariu, Octavian ; Duran, Daniel ; Erson-Omay, E. Zeynep ; Kaulen, Leon D. ; Lee, Tong Ihn ; Abraham, Brian J. ; Simon, Matthias ; Krischek, Boris ; Timmer, Marco ; Goldbrunner, Roland ; Omay, S. Bülent ; Baranoski, Jacob ; Baran, Burçin ; Carrión-Grant, Geneive ; Bai, Hanwen ; Mishra-Gorur, Ketu ; Schramm, Johannes ; Moliterno, Jennifer ; Vortmeyer, Alexander ; Bilgüvar, Kaya ; Yasuno, Katsuhito ; Young, Richard A. ; Günel, Murat. / Integrated genomic analyses of de novo pathways underlying atypical meningiomas. In: Nature communications. 2017 ; Vol. 8.
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