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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sally R Williams - , Harvard Medical School (HMS) (Author)
  • Tareq A Juratli - , Massachusetts General Hospital, Harvard Medical School (HMS) (Author)
  • Brandyn A Castro - , Harvard Medical School (HMS) (Author)
  • Tyler T Lazaro - , Harvard Medical School (HMS) (Author)
  • Corey M Gill - , Harvard Medical School (HMS) (Author)
  • Naema Nayyar - , Harvard Medical School (HMS) (Author)
  • Matthew R Strickland - , Harvard Medical School (HMS) (Author)
  • Melanie Babinski - , Harvard Medical School (HMS) (Author)
  • Sarah E Johnstone - , Harvard Medical School (HMS) (Author)
  • Matthew P Frosch - , Harvard Medical School (HMS) (Author)
  • Ian M Silverman - , Ignyta, Inc. (Author)
  • Heather A Ely - , Ignyta, Inc. (Author)
  • Alexander B Kaplan - , Harvard Medical School (HMS) (Author)
  • Megan R D'Andrea - , Harvard Medical School (HMS) (Author)
  • Ivanna V Bihun - , Harvard Medical School (HMS) (Author)
  • Kaitlin Hoang - , Harvard Medical School (HMS) (Author)
  • Emily Batchelor - , Harvard Medical School (HMS) (Author)
  • Jason Christiansen - , Ignyta, Inc. (Author)
  • Daniel P Cahill - , Harvard Medical School (HMS) (Author)
  • Frederick G Barker - , Harvard Medical School (HMS) (Author)
  • Priscilla K Brastianos - , Harvard Medical School (HMS) (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)562-567
Number of pages6
JournalJournal of neurological surgery : Part B, Skull base
Volume80
Issue number6
Publication statusPublished - Dec 2019
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC6864425
Scopus 85075346844

Keywords

Sustainable Development Goals