Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma
Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma
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DOI：
10.1093/neuonc/nov316
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发表时间：
2016-05-01
期刊：
影响因子：
15.9
通讯作者：
Santagata, Sandro
中科院分区：
文献类型：
--
作者：
Abedalthagafi, Malak;Bi, Wenya Linda;Santagata, Sandro
背景资料。脑膜瘤是成人最常见的原发颅内肿瘤。脑膜瘤中SMO和AKT1突变的发现增加了对一些患者进行靶向治疗的可能性。临床队列中此类突变的频率和脑膜瘤中其他可操作突变的存在是重要的定义。我们使用高分辨率阵列比较基因组杂交来前瞻性地表征150例脑膜瘤的拷贝数变化，然后表征这些样本中AKT1、KLF4、NF2、PIK3CA、SMO和TRAF7的突变。类似于以前的报道，我们在非NF2突变脑膜瘤的一个子集中发现了AKT1和SMO突变(即分别类似于9%和类似于6%)。值得注意的是，我们在7%的非NF2突变脑膜瘤中检测到PIK3CA的致癌突变。AKT1、SMO和PIK3CA突变是互斥的。AKT1、KLF4和PIK3CA突变经常与TRAF7突变并存。突变型PIK3CA脑膜瘤的染色体表现为有限的不稳定性，且丰富于颅底。这项工作确定PI3K信号是脑膜瘤患者精确药物试验的重要靶点。
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, similar to 9% and similar to 6%, respectively). Notably, we detected oncogenic mutations in PIK3CA in similar to 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.