Abstract：
Pilocytic astrocytoma (PA), a central nervous system (CNS) World Health Organization grade 1 tumor, is mainly seen in children or young adults aged 5-19. Surgical resection often provides excellent outcomes, but residual tumors may still remain. This low-grade tumor is well recognized for its classic radiological and morphological features; however, some unique molecular findings have been unveiled by the application of next-generation sequencing (NGS). Among the genetic abnormalities identified in this low-grade tumor, increasing evidence indicates that BRAF alterations, especially BRAF fusions, play an essential role in PA tumorigenesis. Among the several fusion partner genes identified in PAs, KIAA1549-BRAF fusion is notably the most common detectable genetic alteration, especially in the cerebellar PAs. Here, we report a case of a young adult patient with a large, right-sided posterior fossa cerebellar and cerebellopontine angle region mass consistent with a PA. Of note, NGS detected a novel GNAI3-BRAF fusion, which results in an in-frame fusion protein containing the kinase domain of BRAF. This finding expands the knowledge of BRAF fusions in the tumorigenesis of PAs, provides an additional molecular signature for diagnosis, and a target for future therapy.
摘要：
毛细胞星形细胞瘤(PA),中枢神经系统（CNS）世界卫生组织1级肿瘤，主要见于5-19岁的儿童或年轻人。手术切除通常提供优异的结果，但残余肿瘤可能仍然存在。这种低度肿瘤因其经典的放射学和形态学特征而广为人知；然而，下一代测序(NGS)的应用揭示了一些独特的分子发现.在这种低度肿瘤中发现的遗传异常中，越来越多的证据表明BRAF改变，尤其是BRAF融合,在PA肿瘤发生中起重要作用。在PAs中鉴定的几个融合伴侣基因中，KIAA1549-BRAF融合是最常见的可检测遗传改变，尤其是在小脑PA中。这里,我们报告了一个年轻的成年患者，右侧后颅窝小脑和小脑桥脑角区域肿块与PA一致。值得注意的是，NGS检测到一种新的GNAI3-BRAF融合，其产生含有BRAF的激酶结构域的框内融合蛋白。这一发现扩展了BRAF融合在PAs肿瘤发生中的知识，为诊断提供了额外的分子特征，和未来治疗的目标。
