Science. 2013 Jan 24. [Epub ahead of print]
Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO.
Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Ozduman K, Avsar T, Li J, Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yilmaz B, Grady C, Tanrikulu B, Bakircioglu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert R, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kiliç T, Lifton RP, Noonan JP, Yasuno K, Günel M.
SourceDepartments of Neurosurgery and Genetics, Yale Program in Brain Tumor Research, Yale School of Medicine, New Haven, CT 06510, USA.
AbstractWe 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 skull base. In contrast, the vast majority of atypical meningiomas were NF2-mutant, showing genomic instability and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting novel avenues for targeted therapeutics.
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