Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas

Sally R. Williams, Tareq A. Juratli, Brandyn A. Castro, Tyler T. Lazaro, Corey M. Gill, Naema Nayyar, Matthew R. Strickland, Melanie Babinski, Sarah E. Johnstone, Matthew P. Frosch, Ian M. Silverman, Heather A. Ely, Alexander B. Kaplan, Megan R. D'andrea, Ivanna V. Bihun, Kaitlin Hoang, Emily Batchelor, Jason Christiansen, Daniel P. Cahill, Frederick G. BarkerPriscilla K. Brastianos

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1, SMO, and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 ×. Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT 1 (E17K) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO (L412F) or a PIK3CA (E545K) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

Original languageEnglish
Pages (from-to)562-567
Number of pages6
JournalJournal of Neurological Surgery, Part B: Skull Base
Issue number6
StatePublished - 2019
Externally publishedYes


  • AKT1
  • fusions
  • genomics
  • meningioma
  • oncology
  • skull base
  • targeted treatment


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