| Literature DB >> 23348505 |
Victoria E Clark1, E Zeynep Erson-Omay, Akdes Serin, Jun Yin, Justin Cotney, Koray Ozduman, Timuçin Avşar, Jie Li, Phillip B Murray, Octavian Henegariu, Saliha Yilmaz, Jennifer Moliterno Günel, Geneive Carrión-Grant, Baran Yilmaz, Conor Grady, Bahattin Tanrikulu, Mehmet Bakircioğlu, Hande Kaymakçalan, Ahmet Okay Caglayan, Leman Sencar, Emre 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.
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 AKT1(E17K), 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.Entities:
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Year: 2013 PMID： 23348505 PMCID： PMC4808587 DOI： 10.1126/science.1233009
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728