成纤维细胞生长因子受体 1 突变与儿童和青年患者低级别胶质瘤自发性出血的相关性。
Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients.
机构信息
1Department of Neurosurgery, Hokkaido University School of Medicine, Kita-ku, Sapporo.
2Department of Surgical Pathology, Hokkaido University Hospital, Kita-ku, Sapporo; and.
出版信息
J Neurosurg. 2020 Feb 14;134(3):733-741. doi: 10.3171/2019.12.JNS192155. Print 2021 Mar 1.
OBJECTIVE
The authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.
METHODS
Patients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors' institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.
RESULTS
Among 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.
CONCLUSIONS
Although the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.
目的
本研究旨在探讨儿童和青年自发性出血低级别胶质瘤（LGG）患者的遗传改变。
方法
对在本机构接受治疗的年龄小于 30 岁、病理诊断为世界卫生组织（WHO）1 级或 2 级胶质瘤的患者进行回顾性研究。对 BRAF V600E、FGFR1 N546/K656、IDH1 R132、IDH2 R172 和 KIAA1549-BRAF（K-B）融合基因改变进行鉴定，并记录肿瘤自发性出血的存在情况。
结果
在 66 例患者（39 例为 WHO 1 级肿瘤，27 例为 2 级肿瘤）中，基因分析显示 18 例（27.3%）存在 K-B 融合，14 例（21.2%）存在 BRAF V600E 突变，8 例（12.1%）存在 IDH1/2 突变，4 例（6.1%）存在 FGFR1 突变。5 例（7.6%）患者出现自发性出血；其中 4 例存在 FGFR1 突变，1 例存在 K-B 融合。单因素分析显示，FGFR1 突变和间脑位置与自发性出血显著相关。在包括视神经、下丘脑和丘脑在内的 19 例间脑病例中，FGFR1 突变与自发性出血显著相关（p<0.001）。4 例 FGFR1 突变病例的结果如下：1）1 例 2 岁女性患者患有毛细胞型星形细胞瘤（PMA），携带 FGFR1 K656E 突变，表现为脑室出血（IVH）；2）1 例 6 岁男性患者患有 PMA，携带 FGFR1 K656E 和 D652G 突变，表现为肿瘤内出血（ITH）；3）1 例 4 岁女性患者患有弥漫性星形细胞瘤，携带 FGFR1 K656M 和 D652G 突变，表现为 IVH；4）1 例年轻成年患者患有毛细胞型星形细胞瘤，携带 FGFR1 N546K 突变，在观察 7 年后出现迟发性 ITH 和 IVH。
结论
尽管机制尚不清楚，但 FGFR1 突变与儿童和青年 LGG 的自发性出血有关。
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