Document Detail

Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.
MedLine Citation:
PMID:  23348505     Owner:  NLM     Status:  MEDLINE    
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.
Victoria E Clark; 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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  339     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-01     Completed Date:  2013-03-07     Revised Date:  2014-04-23    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1077-80     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Brain Neoplasms / classification,  genetics*,  pathology
Chromosomes, Human, Pair 22 / genetics
DNA Mutational Analysis
Genes, Neurofibromatosis 2
Genomic Instability
Kruppel-Like Transcription Factors / genetics*
Meningeal Neoplasms / classification,  genetics*,  pathology
Meningioma / classification,  genetics*,  pathology
Middle Aged
Neoplasm Grading
Proto-Oncogene Proteins c-akt / genetics*
Receptors, G-Protein-Coupled / genetics*
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / genetics*
Grant Support
T32 GM007205/GM/NIGMS NIH HHS; T32GM07205/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/GKLF protein; 0/Kruppel-Like Transcription Factors; 0/Receptors, G-Protein-Coupled; 0/SMO protein, human; 0/TRAF7 protein, human; 0/Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; EC protein, human; EC Proteins c-akt
Comment In:
Cancer Discov. 2013 Mar;3(3):OF13   [PMID:  23475883 ]
Neurosurgery. 2013 Aug;73(2):N22-4   [PMID:  23867274 ]

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