Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO Journal Article
| Authors: | 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.; Sencar, L.; Ceyhun, E.; Atik, A. F.; Bayri, Y.; Bai, H.; Kolb, L. E.; Hebert, R. M.; Omay, S. B.; Mishra-Gorur, K.; Choi, M.; Overton, J. D.; Holland, E. C.; Mane, S.; State, M. W.; Bilgüvar, K.; Baehring, J. M.; Gutin, P. H.; Piepmeier, J. M.; Vortmeyer, A.; Brennan, C. W.; Pamir, M. N.; Kiliç, T.; Lifton, R. P.; Noonan, J. P.; Yasuno, K.; Günel, M. |
| Article Title: | Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO |
| 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. |
| Keywords: | signal transduction; protein kinase b; adult; controlled study; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; mutation; brain tumor; brain neoplasms; chromosome; gene; signaling; sonic hedgehog protein; phosphatidylinositol 3 kinase; genome analysis; brain; meningeal neoplasms; genomic instability; proto-oncogene proteins c-akt; kruppel-like transcription factors; genomics; chromosomal instability; genome; meningioma; dna mutational analysis; tumor; ubiquitin protein ligase e3; chromosome loss; erinaceidae; smoothened protein; receptors, g-protein-coupled; skull base tumor; kruppel like factor 4; akt1 gene; chromosome 22; chromosomes, human, pair 22; cerebellum tumor; genes, neurofibromatosis 2; neoplasm grading; klf4 gene; smo gene; traf7 gene; tumor necrosis factor receptor-associated peptides and proteins |
| Journal Title: | Science |
| Volume: | 339 |
| Issue: | 6123 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2013-03-01 |
| Start Page: | 1077 |
| End Page: | 1080 |
| Language: | English |
| DOI: | 10.1126/science.1233009 |
| PUBMED: | 23348505 |
| PROVIDER: | scopus |
| PMCID: | PMC4808587 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 1 April 2013" - "CODEN: SCIEA" - "Source: Scopus" |
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