Oncogenic PI3K mutations are as common as<i>AKT1</i>and<i>SMO</i>mutations in meningioma

TLDR

Meningiomas are the most common primary intracranial tumor in adults, and the discovery of SMO and AKT1 mutations has suggested potential targeted therapies. The study aims to determine the frequency of actionable mutations, including PIK3CA, in clinical meningioma cohorts and to highlight PI3K signaling as a target for precision medicine. High‑resolution array‑comparative genomic hybridization was applied to 150 meningiomas, followed by mutation analysis of AKT1, KLF4, NF2, PIK3CA, SMO, and TRAF7. AKT1 and SMO mutations were found in about 9 % and 6 % of non‑NF2‑mutant meningiomas, PIK3CA mutations occurred in ~7 %, and these mutations were mutually exclusive but often co‑occurred with TRAF7 mutations; PIK3CA‑mutant tumors exhibited limited chromosomal instability and skull‑base enrichment.

Abstract

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