成人大脑局限性胶质瘤中可操作的 FGFR1 和 BRAF 突变。
Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas.
机构信息
Department of Health Sciences, Università del Piemonte Orientale, 28100, Novara, Italy.
Pathology Unit, Maggiore Della Carità Hospital, 28100, Novara, Italy.
出版信息
J Neurooncol. 2019 Nov;145(2):241-245. doi: 10.1007/s11060-019-03306-9. Epub 2019 Oct 31.
PURPOSE
Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas.
METHODS
Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced.
RESULTS
FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated.
CONCLUSIONS
We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.
目的
局灶性神经胶质瘤——毛细胞型星形细胞瘤（PA）、神经节细胞瘤（GG）、室管膜瘤（EP）——多为低级别肿瘤，但可能进展为间变，有时由于解剖位置深，手术可能具有挑战性。由于 MAPK 通路改变的高频率以及针对 FGFR1 和 BRAF 突变肿瘤的靶向治疗的可用性，我们在一组成人局灶性神经胶质瘤中研究了这些突变热点。
方法
从两个机构的数据库中回顾性确定诊断为 PA、GG、EP 和 DNET 的成年患者（>15 岁）。从福尔马林固定石蜡包埋或冷冻样本中提取基因组 DNA，并对包括 FGFR1 的外显子 546 和 656 以及 BRAF 的 V600 在内的密码子进行测序。
结果
在 108 例 PA 中有 15 例发现 FGFR1 突变，在视神经通路中尤为常见（6/9 与 9/108；p=10）。FGFR1 在 75 例 2 级 GG 中有 3 例突变，在 7 例 3 级 GG 中有 2 例突变（p=0.05），在 1 例 DNET 中有 1 例，在 100 例 EP 中有 2 例。我们发现 3 例 PA 存在 BRAF pVal600Glu 突变，108 例中存在 6 例 p.Thr599_Val600insThr 突变。p.Val600Glu 突变见于 14 例 75 例 2 级 GG 中。没有 EP 存在 BRAF 突变。
结论
我们报告了可采取行动的靶点，包括视神经通路中常见的 FGFR1 突变，这使它们成为抗 FGFR 治疗的理想候选物，以及 PA 中的 BRAF 非典型突变。
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