Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO

Victoria E. Clark, E. Zeynep Erson-Omay, Akdes Serin, Jun Yin, Justin Cotney, Koray Özduman, Timuçin Avşar, Jie Li, Phillip B. Murray, Octavian Henegariu, Saliha Yilmaz, Jennifer Moliterno Günel, Geneive Carrión-Grant, Baran Yilmaz, Conor Grady, Bahattin Tanrikulu, Mehmet Bakircioǧlu, Hande Kaymakçalan, Ahmet Okay Caglayan, Leman SencarEmre Ceyhun, A. Fatih Atik, Yaşar Bayri, Hanwen Bai, Luis E. Kolb, Ryan M. Hebert, S. Bulent Omay, Ketu Mishra-Gorur, Murim Choi, John D. Overton, Eric C. Holland, Shrikant Mane, Matthew W. State, Kaya Bilgüvar, Joachim M. Baehring, Philip H. Gutin, Joseph M. Piepmeier, Alexander Vortmeyer, Cameron W. Brennan, M. Necmettin Pamir, Türker Kiliç, Richard P. Lifton, James P. Noonan, Katsuhito Yasuno, Murat Günel

Research output: Contribution to journalArticle

360 Scopus citations

Abstract

We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1E17K, a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ∼5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive - nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)1077-1080
Number of pages4
JournalScience
Volume339
Issue number6123
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

ASJC Scopus subject areas

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    Clark, V. E., Erson-Omay, E. Z., Serin, A., Yin, J., Cotney, J., Özduman, K., Avşar, T., Li, J., Murray, P. B., Henegariu, O., Yilmaz, S., Günel, J. M., Carrión-Grant, G., Yilmaz, B., Grady, C., Tanrikulu, B., Bakircioǧlu, M., Kaymakçalan, H., Caglayan, A. O., ... Günel, M. (2013). Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science, 339(6123), 1077-1080. https://doi.org/10.1126/science.1233009