LGG-03. NEW INSIGHTS INTO PEDIATRIC LOW-GRADE GLIOMAS IN SAUDI ARABIA REVEALED THROUGH GENETIC PROFILING SINGLE CENTER EXPERIENCE

OBJECTIVE: Gliomas account for ≥ 50% of childhood central nervous neoplasms and can be subdivided into low-grade (LGG) and high grade gliomas (HGG). We performed comprehensive genomic profiling on 20 Saudi pediatric LGG (pLGG) patients to identify tumor associated genetic abnormalities. The identification of these events can inform prognostic, and therapeutic decision-making. METHODS: This retrospective study was performed on 20 children (<16 y) newly diagnosed with pathologically confirmed LGG. We reviewed the molecular, clinical and therapeutic aspects and the treatment outcome of pLGG patients. Next generation sequencing was performed using the Oncomine Comprehensive Assay v3 system from formalin-fixed paraffin embedded (FFPE) tumor samples. Data were analyzed using the SPSS statistical package version 23. RESULTS: We detected genomic alterations (GAs) in all of the tumors, averaging 4.52 ± 2.11 GAs per patient. BRAF was the most commonly altered gene (75.0%, 15/20 cases). Other frequently mutated genes included ATM 15% (3/20), RNF43 15 % (3/20), RAD51C 20% (4/20) and Notch2 20% (4/20). Casually altered genes (observed in less than 3 patients) included FANCD2, FGFR1, BRCA2, CDC4, KIF5B, RET, AKAP, SLX4, MSH6, NTRK, CCDC170, MLH1, AGK, PDGFRB, EIF3B,FGFR2, CDKN2A/B, PTCH1, SETD2, SLX4, MSH6 NTRK and CDK4. Interestingly, we identified a novel gene fusion of GOPC (Fig)-ROS1 in a 10-year old patient that lacked BRAF fusions. Midline tumor analysis revealed a left parietal mass with vasogenic edema. The patient received surgical resection with excellent postoperative recovery and no neurological deficit. No adjuvant chemotherapy or radiation therapy was required and the patient is stable with no tumor recurrence. CONCLUSIONS: We provide comprehensive genomic profiling of Saudi pLGGs that promote diagnostic accuracy and enhance clinical decision-making. Additionally, GOPC1-ROS1 may be a biomarker to identify pLGG patients that will benefit from Target therapy