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Nat Genet DOI:10.1038/ng.2526

Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.

Publication TypeJournal Article
Year of Publication2013
AuthorsBrastianos, PK, Horowitz, PM, Santagata, S, Jones, RT, McKenna, A, Getz, G, Ligon, KL, Palescandolo, E, Van Hummelen, P, Ducar, MD, Raza, A, Sunkavalli, A, MacConaill, LE, Stemmer-Rachamimov, AO, Louis, DN, Hahn, WC, Dunn, IF, Beroukhim, R
JournalNat Genet
Date Published2013 Mar
KeywordsBase Sequence, Brain Neoplasms, Genomics, Humans, Meningioma, Mutation, Neurofibromin 2, Proto-Oncogene Proteins c-akt, Receptors, G-Protein-Coupled, Smoothened Receptor

Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of all meningiomas, but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas had simple genomes, with fewer mutations, rearrangements and copy-number alterations than reported in other tumors in adults. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements, including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers in an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets.


Alternate JournalNat. Genet.
PubMed ID23334667
PubMed Central IDPMC3739288
Grant ListK08 CA122833 / CA / NCI NIH HHS / United States
K08 NS064168 / NS / NINDS NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
K12 CA090354-11 / CA / NCI NIH HHS / United States