Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas
Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas
复制标题
DOI：
10.1055/s-0038-1676821
复制
发表时间：
2019-12-01
影响因子：
0.9
通讯作者：
Brastianos, Priscilla K.
中科院分区：
文献类型：
--
作者：
Williams, Sally R.;Juratli, Tareq A.;Brastianos, Priscilla K.
目的后颅窝脑膜瘤是一种具有手术挑战性的肿瘤，具有较高的发病率和死亡率。我们试图调查临床上可操作的突变在后颅窝脑膜瘤中的解剖分布，以便于识别适合于系统靶向治疗试验的患者。方法使用Illumina NextSeq 500对61例后颅窝脑膜瘤的临床靶向AKT1、SMO和PIK3CA突变进行定向测序，目标深度为500倍。Archer FusionPlex小组进一步询问了样本中与癌症相关的53种RNA融合，以检测基因重排。结果AKT1(E17K)突变5例，占8.2%，其中枕大孔区4例，桥小脑角区1例。相比之下，后颅窝肿瘤中没有SMO(L412F)或PIK3CA(E545K)突变。值得注意的是，大多数枕大孔脑膜瘤(4/7，57%)含有AKT1突变。此外，在任何病例中都没有检测到常见的临床靶向基因融合。结论枕骨大孔区脑膜瘤中存在AKT1E17K突变，因此有可能接受靶向药物治疗。枕大孔脑膜瘤的基因分型可能会提供更多的治疗选择，并指导他们的治疗决策过程。
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 x . 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.