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Review
. 2020 Feb 21;8(1):21.
doi: 10.1186/s40478-020-00898-6.

FGFR- gene family alterations in low-grade neuroepithelial tumors

Tejus A Bale  1
Affiliations
Review

FGFR- gene family alterations in low-grade neuroepithelial tumors

Tejus A Bale. Acta Neuropathol Commun. .

Abstract

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.

Keywords: FGFR-fusion; FGFR-mutant; Low grade glioma; Low grade glioneuronal tumor.

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Conflict of interest statement

The author has no competing interests to declare.

Figures

Fig. 1
Fig. 1
Summary of common FGFR alterations in brain tumors. Some alterations are strongly associated with low grade neuroepithelial lesions: FGFR1-TKD, FGFR1-TACC1 fusion, FGFR2-CTNNA3 fusion. Others (including FGFR1 hotspot mutations and FGFR3-TACC3 fusions) are described in low-grade as well as high-grade tumors, requiring cautious interpretation when encountered in histologic LGNTs
Fig. 2
Fig. 2
Histologic features of FGFR-altered LGNTs. Three examples of LGNTs bearing characteristic FGFR-alteration are shown: DNET with FGFR1- TKD (a, b), EVN with FGFR1-TACC1 fusion (c, d), and PLNTY with FGFR2-CTNNA3 fusion (e, f). Note that while histologic features of each lesion met diagnostic criteria in keeping with a specific entity, LGNTs share many overlapping histologic features including bland neurocytic/ oligodedroglioma-like nuclear features and of lack of significant proliferative or mitotic activity
See this image and copyright information in PMC

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