FGFR- gene family alterations in low-grade neuroepithelial tumors

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.