Harmanci, Akdes Serin, Youngblood, Mark W., Clark, Victoria E., Coskun, Sueleyman, Henegariu, Octavian, Duran, Daniel ORCID: 0000-0001-6888-252X, Erson-Omay, E. Zeynep, Kaulen, Leon D., Lee, Tong Ihn, Abraham, Brian J., Simon, Matthias, Krischek, Boris, Timmer, Marco, Goldbrunner, Roland, Omay, S. Buelent, Baranoski, Jacob, Baran, Burcin, Carrion-Grant, Geneive, Bai, Hanwen, Mishra-Gorur, Ketu, Schramm, Johannes, Moliterno, Jennifer, Vortmeyer, Alexander O., Bilguevar, Kaya, Yasuno, Katsuhito ORCID: 0000-0002-3606-532X, Young, Richard A. and Guenel, Murat (2017). Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Harmanci, Akdes SerinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Youngblood, Mark W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clark, Victoria E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coskun, SueleymanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henegariu, OctavianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duran, DanielUNSPECIFIEDorcid.org/0000-0001-6888-252XUNSPECIFIED
Erson-Omay, E. ZeynepUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaulen, Leon D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Tong IhnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abraham, Brian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krischek, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmer, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldbrunner, RolandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Omay, S. BuelentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baranoski, JacobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baran, BurcinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carrion-Grant, GeneiveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bai, HanwenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mishra-Gorur, KetuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schramm, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moliterno, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vortmeyer, Alexander O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bilguevar, KayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yasuno, KatsuhitoUNSPECIFIEDorcid.org/0000-0002-3606-532XUNSPECIFIED
Young, Richard A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, MuratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-239797
DOI: 10.1038/ncomms14433
Journal or Publication Title: Nat. Commun.
Volume: 8
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CENTRAL-NERVOUS-SYSTEM; SEQUENCING DATA; SOMATIC MUTATIONS; CANCER; TUMORS; CLASSIFICATION; EXPRESSION; ASSOCIATION; FRAMEWORK; POLYCOMBMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23979

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