Targeted sequencing of SMO and AKT1 in anterior skull base meningiomas

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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.

ABBREVIATIONS 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.
Article Information

Contributor Notes

Correspondence Fred G. Barker II, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit St., Yawkey 9E, Boston, MA 02114. email: barker@helix.mgh.harvard.edu.INCLUDE WHEN CITING Published online November 25, 2016; DOI: 10.3171/2016.8.JNS161076.

Dr. Strickland and Mr. Gill contributed equally to this work. Drs. Cahill, Brastianos, and Barker share senior authorship.

Disclosures Dr. Thiede reports that he has ownership in AgenDix GmbH. Dr. Brastianos reports that she is a consultant for Genentech and has received speaker's honoraria from Merck. Dr. Cahill reports that he has received speaker's honoraria from Merck.

© AANS, except where prohibited by US copyright law.

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