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Neuro Oncol. 2016 May;18(5):649-55. doi: 10.1093/neuonc/nov316. Epub 2016 Jan 28.

Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (M.A., P.H.M., R.B., M.L.L., S.H.R., R.D.F., K.L.L., A.H.L., S.S.); Department of Pathology, King Fahad Medical City, Riyadh, Saudi Arabia (M.A.); King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia (M.A.); Harvard Medical School, Boston, Massachusetts (M.A., A.A.A., D.D.-S., P.K.B., D.A.R., P.Y.W., O.A.-M., S.H.R., R.D.F., K.L.L., A.H.L., B.M.A., I.F.D., R.B., S.S.); Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts (W.L.B., O.A.-M., I.F.D.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (A.A.A., B.M.A.); Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (P.K.A.); Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts (D.D.-S.); Center for Cancer Genomic Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts (A.R.T., P.V.H.); Department of Neuro-Oncology, Massachusetts General Hospital, Boston, Massachusetts (P.K.B.); Center of Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (D.A.R., P.Y.W, R.B.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (K.L.L., R.B.); Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA (S.S.).

Abstract

BACKGROUND:

Meningiomas are the most common primary intracranial tumor in adults. Identification of SMO and AKT1 mutations in meningiomas has raised the possibility of targeted therapies for some patients. The frequency of such mutations in clinical cohorts and the presence of other actionable mutations in meningiomas are important to define.

METHODS:

We used high-resolution array-comparative genomic hybridization to prospectively characterize copy-number changes in 150 meningiomas and then characterized these samples for mutations in AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7.

RESULTS:

Similar to prior reports, we identified AKT1 and SMO mutations in a subset of non-NF2-mutant meningiomas (ie, ∼9% and ∼6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in ∼7% of non-NF2-mutant meningiomas. AKT1, SMO, and PIK3CA mutations were mutually exclusive. AKT1, KLF4, and PIK3CA mutations often co-occurred with mutations in TRAF7. PIK3CA-mutant meningiomas showed limited chromosomal instability and were enriched in the skull base.

CONCLUSION:

This work identifies PI3K signaling as an important target for precision medicine trials in meningioma patients.

KEYWORDS:

AKT1; NF2; PIK3CA; SMO; aCGH; meningioma; molecular pathology

Comment in

PMID:
26826201
PMCID:
PMC4827048
DOI:
10.1093/neuonc/nov316
[Indexed for MEDLINE]
Free PMC Article

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