Chen Xin, Pan Changcun, Zhang Peng, Xu Cheng, Sun Yu, Yu Hai, Wu Yuliang, Geng Yibo, Zuo Pengcheng, Wu Zhen, Zhang Junting, Zhang Liwei
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantanxili 6, Dongcheng District, Beijing 100050, China; China National Clinical Research Center for Neurological Disease, Tiantanxili 6, Dongcheng District, Beijing 100050, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantanxili 6, Dongcheng District, Beijing 100050, China; China National Clinical Research Center for Neurological Disease, Tiantanxili 6, Dongcheng District, Beijing 100050, China.
J Clin Neurosci. 2017 Dec;46:50-57. doi: 10.1016/j.jocn.2017.09.014. Epub 2017 Oct 3.
BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.
BRAF V600E突变是小儿低级别胶质瘤的进展因素。此外，高比例的小儿脑干神经节胶质瘤存在BRAF V600E突变。然而，其临床意义，包括生物标志物与神经节胶质瘤临床特征（尤其是脑干神经节胶质瘤）之间的可能联系尚不清楚。为了确定预测脑干神经节胶质瘤临床结局的潜在分子特征，对28例世界卫生组织（WHO）I级脑干神经节胶质瘤的回顾性队列进行了BRAF V600E、异柠檬酸脱氢酶1（IDH1）R132H、异柠檬酸脱氢酶2（IDH2）R172K突变、端粒酶逆转录酶（TERT）C228T/C250T启动子突变、组蛋白H3.3A（H3F3A）K27M突变和O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）甲基化分析。使用3D Slicer软件精确计算肿瘤体积。对这些患者的临床数据进行回顾性分析。在BRAF V600E突变的肿瘤中，肿瘤复发率明显快于野生型组（p=0.001）。此外，与野生型相比，BRAF V600E突变组的无进展生存期（PFS）更短（p=0.012）。多因素分析未发现任何因素是独立的预后因素；然而，肿瘤复发率较快的患者有PFS缩短风险增加的强烈趋势（风险比[HR]=1.027，p=0.056）。无法进行统计分析以评估影响总生存期（OS）的因素。这些数据表明，BRAF V600E可预测显微手术后脑干神经节胶质瘤的复发率，针对BRAF V600E的治疗可能是显微手术后携带BRAF V600E突变患者有前景的早期干预措施。
