Targeted sequencing of SMO and AKT1 in anterior skull base meningiomas

J Neurosurg. 2017 Aug;127(2):438-444. doi: 10.3171/2016.8.JNS161076. Epub 2016 Nov 25.

Abstract

OBJECTIVE Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove. Meningiomas with an SMO mutation presented with significantly larger tumor volume (70.6 ± 36.3 cm3) compared with AKT1-mutated (18.2 ± 26.8 cm3) and wild-type (22.7 ± 23.9 cm3) meningiomas, respectively. CONCLUSIONS Combined, these data demonstrate clinically actionable mutations in 30% of anterior skull base meningiomas and suggest an association between SMO mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high yield in anterior skull base meningiomas with available surgical tissue.

Keywords: AUC = area under the curve; CSA = cross-sectional area; FFPE = formalin-fixed paraffin-embedded; GTR = gross-total resection; ROC = receiver operating characteristic; SHH = sonic hedgehog; WT = wild-type; clinically actionable; meningioma; oncology; skull base; targeted sequencing.

Publication types

  • Comment

MeSH terms

  • Humans
  • Meningeal Neoplasms*
  • Meningioma*
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Skull Base
  • Smoothened Receptor

Substances

  • SMO protein, human
  • Smoothened Receptor
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt