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

Autor:	Williams SR; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Juratli TA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Division of Neuro-Oncology, Department of Neurology, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Castro BA; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Lazaro TT; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Gill CM; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Nayyar N; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Strickland MR; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Babinski M; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Johnstone SE; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Frosch MP; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Silverman IM; Ignyta Inc., San Diego, California, United States., Ely HA; Ignyta Inc., San Diego, California, United States., Kaplan AB; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., D'Andrea MR; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Bihun IV; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Hoang K; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Batchelor E; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Christiansen J; Ignyta Inc., San Diego, California, United States., Cahill DP; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Barker FG 2nd; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States., Brastianos PK; Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Division of Neuro-Oncology, Department of Neurology, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Division of Hematology/Oncology, Department of Medicine, Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Jazyk:	angličtina
Zdroj:	Journal of neurological surgery. Part B, Skull base [J Neurol Surg B Skull Base] 2019 Dec; Vol. 80 (6), pp. 562-567. Date of Electronic Publication: 2019 Jan 10.
DOI:	10.1055/s-0038-1676821
Abstrakt:	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. Competing Interests: Conflict of Interest Dr. Cahill report honoraria and travel expenses from Merck. He also reports being a consultant to Lilly outside the submitted work. Dr. Silverman reports being a stockholder for Incyte. (© Thieme Medical Publishers.)
Databáze:	MEDLINE
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