FGFR1 gene mutation as a potential risk factor for spontaneous intracranial hemorrhage in pediatric low grade glioma patients

Fibroblast Growth Factor Receptor 1 (FGFR1) mutations have been associated with poorer prognoses in pediatric CNS tumor patients. A recent study highlighted a link between FGFR1 mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all their patients with an FGFR1 alteration experienced hemorrhage at some point during their course of treatment. The current study examined fifty out of sixty-seven pediatric patients with low grade gliomas that had genomic testing between 2011-2022 at our institution to determine whether a correlation exists between FGFR1 mutations and spontaneous ICH. We found that of the fifty patients with genomic data, seven (14%) experienced ICH, an additional spontaneous hemorrhage was recorded, however, no genomic testing was performed for this case. Five of the seven patients (71.4%) had an FGFR1 modification. In our patient population, six expressed a detectable FGFR1 mutation (66.7% [4/6] had N546K alteration, 16.7% [1/6] FGFR1 exons duplication, and 16.7% [1/6] had a variant of unknown significance). The patient with the FGFR1 variant of unknown significance had no reported spontaneous hemorrhage. Statistical analysis found a significant association between FGFR1 and spontaneous intracranial hemorrhage (p-value = <0.0001). In the patient population, all cases of PTPN11 alterations (n=3) co-occurred with FGFR1 mutations. Our case series highlights this link between the FGFR1 mutation and spontaneous intracranial hemorrhage in pediatric Low-Grade Gliomas.