TB-02: UPFRONT, REAL-TIME TUMOR AND GERMLINE SEQUENCING OF PEDIATRIC BRAIN TUMOR PATIENTS: THE UCSF EXPERIENCE

BACKGROUND: Molecular profiling is revolutionizing cancer diagnostics beyond gross morphological evaluation and leading to personalized therapeutic approaches. Herein, we describe our experience performing targeted sequencing for 21 pediatric neuro-oncology patients. METHODS: We sequenced 510 cancer-associated genes in DNA extracted from micro-dissected tumor tissue and peripheral blood using a standardized bioinformatics pipeline to identify germline and somatic mutations and copy number changes. Results were then discussed at a standing multi-disciplinary molecular tumor board to identify clinically relevant alterations. RESULTS: Between June 2015 and January 2016, genomic profiling was performed on 21 brain tumors from pediatric patients, including 3 low-grade gliomas, 9 high-grade gliomas, 5 medulloblastomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, and 1 choroid plexus carcinoma. In 13 cases (62%), results impacted patient management by 1) clarifying diagnosis, 2) identifying previously unsuspected pathogenic germline mutations, or 3) detecting somatic alterations that can be targeted by existing drugs. Four diagnoses changed, including a high- to low-grade glioma and medulloblastoma to pineoblastoma. Nine patients without known family history had germline mutations including 2 patients with high-grade gliomas and novel MUTYH germline mutations. Two patients required treatment modification, including a patient with germline TP53 alteration whose plan for radiation was stopped. Targetable mutations were identified in 9 (43%) patients, including PDGFRA, AKT3, and CDK4 amplifications in one glioblastoma patient. CONCLUSIONS: Our experience demonstrates the impact of molecular profiling on diagnosis and treatment of pediatric brain tumors and confirms its feasibility for upfront use at the time of diagnosis.