Abedalthagafi Malak, Bi Wenya Linda, Aizer Ayal A, Merrill Parker H, Brewster Ryan, Agarwalla Pankaj K, Listewnik Marc L, Dias-Santagata Dora, Thorner Aaron R, Van Hummelen Paul, Brastianos Priscilla K, Reardon David A, Wen Patrick Y, Al-Mefty Ossama, Ramkissoon Shakti H, Folkerth Rebecca D, Ligon Keith L, Ligon Azra H, Alexander Brian M, Dunn Ian F, Beroukhim Rameen, Santagata Sandro
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.).
Neuro Oncol. 2016 May;18(5):649-55. doi: 10.1093/neuonc/nov316. Epub 2016 Jan 28.
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.
脑膜瘤是成人最常见的原发性颅内肿瘤。脑膜瘤中SMO和AKT1突变的鉴定增加了某些患者进行靶向治疗的可能性。确定这些突变在临床队列中的频率以及脑膜瘤中其他可操作突变的存在情况很重要。
我们使用高分辨率阵列比较基因组杂交技术对150例脑膜瘤的拷贝数变化进行前瞻性表征，然后对这些样本进行AKT1、KLF4、NF2、PIK3CA、SMO和TRAF7突变的表征。
与先前报道相似，我们在一部分非NF2突变型脑膜瘤中鉴定出AKT1和SMO突变（即分别约为9%和6%）。值得注意的是，我们在约7%的非NF2突变型脑膜瘤中检测到PIK3CA的致癌突变。AKT1、SMO和PIK3CA突变相互排斥。AKT1、KLF4和PIK3CA突变常与TRAF7突变同时出现。PIK3CA突变型脑膜瘤显示出有限的染色体不稳定性，且在颅底富集。
这项工作确定PI3K信号通路是脑膜瘤患者精准医学试验的重要靶点。
