Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients

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OBJECTIVE

The authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.

METHODS

Patients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors’ institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.

RESULTS

Among 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.

CONCLUSIONS

Although the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.

ABBREVIATIONS DA = diffuse astrocytoma; DNT = dysembryoplastic neuroepithelial tumor; ITH = intratumoral hemorrhage; IVH = intraventricular hemorrhage; K-B fusion = KIAA1549-BRAF fusion; LGG = low-grade glioma; MAPK = mitogen-activated protein kinase; PA = pilocytic astrocytoma; PCR = polymerase chain reaction; PMA = pilomyxoid astrocytoma; TKD = tyrosine kinase domain; WHO = World Health Organization.
Article Information

Contributor Notes

Correspondence Shigeru Yamaguchi: Hokkaido University Graduate School of Medicine, Sapporo, Japan. yama-shu@med.hokudai.ac.jp.INCLUDE WHEN CITING Published online February 14, 2020; DOI: 10.3171/2019.12.JNS192155.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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