The discovery of fibroblast growth factor receptor (FGFR) gene family alterations as drivers of primary brain tumors has generated significant excitement, both as potential therapeutic targets as well as defining hallmarks of histologic entities. However, FGFR alterations among neuroepithelial lesions are not restricted to high or low grade, nor to adult vs. pediatric-type tumors. While it may be tempting to consider FGFR-altered tumors as a unified group, this underlying heterogeneity poses diagnostic and interpretive challenges. Therefore, understanding the underlying biology of tumors harboring specific FGFR alterations is critical. In this review, recent evidence for recurrent FGFR alterations in histologically and biologically low-grade neuroepithelial tumors (LGNTs) is examined (namely FGFR1 tyrosine kinase domain duplication in low grade glioma, FGFR1-TACC1 fusions in extraventricular neurocytoma [EVN], and FGFR2-CTNNA3 fusions in polymorphous low-grade neuroepithelial tumor of the young [PLNTY]). Additionally, FGFR alterations with less well-defined prognostic implications are considered (FGFR3-TACC3 fusions, FGFR1 hotspot mutations). Finally, a framework for practical interpretation of FGFR alterations in low grade glial/glioneuronal tumors is proposed.

中文翻译：

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低级别神经上皮肿瘤中 FGFR- 基因家族的改变。


成纤维细胞生长因子受体 (FGFR) 基因家族改变作为原发性脑肿瘤驱动因素的发现引起了极大的兴奋，这既可以作为潜在的治疗靶标，也可以定义组织学实体的标志。然而，神经上皮病变中 FGFR 的改变不仅限于高级别或低级别肿瘤，也不限于成人型与儿童型肿瘤。虽然人们很容易将 FGFR 改变的肿瘤视为一个统一的群体，但这种潜在的异质性给诊断和解释带来了挑战。因此，了解具有特定 FGFR 改变的肿瘤的基础生物学至关重要。在这篇综述中，检查了组织学和生物学低级别神经上皮肿瘤（LGNT）中复发性 FGFR 改变的最新证据（即低级别神经胶质瘤中的 FGFR1 酪氨酸激酶结构域重复、室外神经细胞瘤 [EVN] 中的 FGFR1-TACC1 融合以及 FGFR2-年轻多形性低级别神经上皮肿瘤中的 CTNNA3 融合 [PLNTY]）。此外，还考虑了对预后影响不太明确的 FGFR 改变（FGFR3-TACC3 融合、FGFR1 热点突变）。最后，提出了一个低级别胶质细胞/胶质神经元肿瘤中 FGFR 改变的实际解释框架。