GENE-13. YEAR ONE IN THE MOLECULAR ERA OF PEDIATRIC BRAIN TUMOR DIAGNOSIS: APPLICATION OF UNIVERSAL CLINICAL TARGETED SEQUENCING IN AN UNSELECTED COHORT OF CHILDREN

INTRODUCTION: The 2016 revision of the WHO classification of CNS tumors defines molecular subtypes and diagnosis in addition to histopathology. However, there is not an established standard diagnostic test or panel. We evaluated the universal application of a next-generation sequencing(NGS) panel in an unselected single-institution cohort of pediatric brain tumor patients. METHODS: We prospectively sequenced 262 cancer-related genes using a clinical laboratory-developed NGS platform (UW-Oncoplex) in all pediatric brain tumors diagnosed at Seattle Children’s Hospital from 11/2015 to 11/2016. Results were reviewed at a molecular tumor board and returned to patients and families with the assistance of a genetic counselor. RESULTS: Ninety patients were included in this study; 64 at diagnosis and 26 at recurrence. Histology included low-grade glioma(38), medulloblastoma(20), high-grade glioma(11), ependymoma(7) and other rare tumors(14). Results were returned for 87/90(97%) at a median of 35 days (range 9–78). Molecular alterations were identified in 69 patients(78%), which were disease defining or modifying in 58(64%). All medulloblastoma were characterized as SHH-activated(7), WNT-activated(1) or non-WNT, non-SHH(12). Only 2 of 8 H3KF3A K28M occured in classic DIPG. Potentially targetable changes were found in 40 patients(46%), most commonly KIAA1549-BRAF translocation(10), BRAFV600E(9), FGFR(9) followed by multiple rare targets each found in <5% of patients(12). To date, six patients have been prescribed targeted therapy based on this testing, two on clinical trial. Potential germline mutations were identified in 33(37%) patients. Of patients tested 5/7 were confirmed to have germline mutations. CONCLUSION: Targeted NGS may be used in clinical practice to diagnose and subclassify pediatric brain tumors, and identify targets for therapy. Efforts to decrease turnaround time and expand panels to include rare variants in pediatric tumors may increase clinical utility.