GENE-21. PEDIATRIC BRAIN TUMORS WITH FGFR1 MUTATIONS: A SERIES OF 14 CASES ASSESSING THE MORPHOLOGIC SPECTRUM AND ASSOCIATED GENETIC ALTERATIONS

BACKGROUND: Recurrent somatic mutations in FGFR1 have been identified in a subset of pediatric glial and glioneuronal tumors. Here we describe the morphologic spectrum and associated genetic alterations in a series of pediatric CNS tumors with activating FGFR1 mutations. METHODS: Genetic alterations in pediatric brain tumors were identified on a clinically validated next-generation sequencing platform that detects single nucleotide variants, insertions and deletions, and selected gene fusions in 262 cancer related genes. The clinical, radiologic, and histologic features of tumors with FGFR1 alterations were reviewed. RESULTS: Sequencing identified activating FGFR1 alterations in fourteen patients, including single nucleotide variants (n=7), tandem duplications (n=4), and FGFR1-TACC1 fusions (n=3). Six tumors with activating single nucleotide variants contained additional genetic alterations, including PTPN11 (n=2), NF1 (n=2), and TP53 (n=1). One contained two different FGFR1 point mutations. Tumors with fusions or tandem duplications lacked other genetic alterations. Tumors displayed varied clinical, radiologic, and histologic features. Age at diagnosis ranged from 3 to 17 years. Tumor locations included spinal cord, thalamus, suprasellar, cerebellum, frontal, parietal, and temporal lobes. Four tumors recurred after initial resection. Ten tumors were low grade, two were not graded, and two were high grade. Morphologic findings included oligodendroglial histology (n=7), infiltration (n=5), vascular proliferation (n=5), eosinophilic granular bodies (n=4) and one case with perivascular nuclear free zones suggestive of ependymoma morphology. CONCLUSIONS: Tumors with activated FGFR1 signaling demonstrate a wide spectrum of clinical, histologic and cooperating genetic features. It will be important to evaluate these factors as potential predictors of response to FGFR targeted therapy.