弓形星形胶质瘤是最常见的儿童脑肿瘤，通常表现为低级别新生物。我们报告了两例合并非典型肿瘤进展的弓形星形胶质瘤。病例1是一名12岁男孩，患有无法切除的射手底部肿瘤，BRAF重排检测为阴性，但携带了BRAF p.V600E突变。他在使用达布拉非尼治疗后，经历了肿瘤缩小和稳定病情。病例2描述了一名6岁男孩的丘脑肿瘤，经过多次切除手术，通过靶向次代测序（NGS）未检测到可操作的驱动因子。全基因组和RNA测序分析鉴定了FGFR1的内部串联重复和RAS通路激活。未来的治疗方案包括FGFR1抑制剂。这些病例显示了儿童脑癌分子诊断逐渐提高的重要性，提倡在目标面板无法提供信息时，早期使用整合全基因组测序和转录组分析。鉴定分子驱动因子可以显著影响治疗决策并改善患者预后。冷泉港实验室出版社。

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-year-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-year-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing (NGS). Whole-genome and RNAseq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.Cold Spring Harbor Laboratory Press.