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


Journal Article

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.

Full Text

Cited Authors

  • Clark, VE; Erson-Omay, EZ; Serin, A; Yin, J; Cotney, J; Ozduman, K; Avşar, T; Li, J; Murray, PB; Henegariu, O; Yilmaz, S; Günel, JM; Carrión-Grant, G; Yilmaz, B; Grady, C; Tanrikulu, B; Bakircioğlu, M; Kaymakçalan, H; Caglayan, AO; Sencar, L; Ceyhun, E; Atik, AF; Bayri, Y; Bai, H; Kolb, LE; Hebert, RM; 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

Published Date

  • March 2013

Published In

Volume / Issue

  • 339 / 6123

Start / End Page

  • 1077 - 1080

PubMed ID

  • 23348505

Pubmed Central ID

  • 23348505

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1233009


  • eng