J Neurol Surg B Skull Base 2019; 80(06): 562-567
DOI: 10.1055/s-0038-1676821
Original Article
Georg Thieme Verlag KG Stuttgart · New York

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

Sally R. Williams*
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Tareq A. Juratli*
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
2  Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
3  Division of Neuro-Oncology, Department of Neurology, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Brandyn A. Castro*
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Tyler T. Lazaro*
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Corey M. Gill
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Naema Nayyar
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Matthew R. Strickland
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Melanie Babinski
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Sarah E. Johnstone
5  Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
,
Matthew P. Frosch
5  Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
,
Ian M. Silverman
6  Ignyta Inc., San Diego, California, United States
,
Heather A. Ely
6  Ignyta Inc., San Diego, California, United States
,
Alexander B. Kaplan
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Megan R. D'Andrea
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Ivanna V. Bihun
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Kaitlin Hoang
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Emily Batchelor
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Jason Christiansen
6  Ignyta Inc., San Diego, California, United States
,
Daniel P. Cahill
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
2  Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Frederick G. Barker II
2  Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Priscilla K. Brastianos
1  Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
3  Division of Neuro-Oncology, Department of Neurology, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
4  Division of Hematology/Oncology, Department of Medicine, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
› Author Affiliations
Funding This work is supported by U.S. NIH 1R21NS099844 (to D. P. Cahill and P. K. Brastianos), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Projektnummer, 401837860 (to Dr. T. Juratli), the Damon Runyon Award (to P. K. Brastianos), Brain Science Foundation (to P. K. Brastianos), and the American Brain Tumor Association (to P. K. Brastianos).
Further Information

Publication History

29 August 2018

13 November 2018

Publication Date:
10 January 2019 (online)

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.

ResultsAKT1 (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.

Note

Portions of this work were presented at the North American Skull Base Society Annual Meeting, New Orleans, Louisiana, United States, March 4, 2017.


* These authors contributed equally to this work.