EPT-20
CLINICAL TARGETED EXOME-BASED SEQUENCING IN COMBINATION WITH GENOME WIDE COPY NUMBER PROFILING: A CLIA CERTIFIED APPROACH FOR PRECISION MEDICINE IN 203 PEDIATRIC BRAIN TUMOR PATIENTS

BACKGROUND: Clinical genomic platforms in CLIA-certified labs are required to identify targetable driver alterations but few reports of such testing and its implementation in routine clinical pediatric oncology practice have been reported. METHODS: PROFILE, a center-wide prospective clinical research study aims to assess feasibility and utility of identifying targetable alterations in adult and pediatric cancer patients. We applied OncoPanel, a multiplexed targeted exome-sequencing platform that surveys 275 cancer genes to identify mutations and copy-number variations. Alterations are tiered, based (Tier 1-4) on clinical significance with Tier 1 alterations being those with well-established evidence confirming clinical utility. OncoPanel also analyzes 90 introns from 30 genes, allowing for detection of rearrangements. Genome-wide copy number profiles were assessed with clinical high-resolution array-CGH. RESULTS: Cancer genomes of 203 pediatric brain tumor patients were profiled across all histological subtypes including117 samples analyzed by Oncopanel, 146 by array CGH, and 60 tumors subjected to both methodologies. Oncopanel revealed clinically relevant alterations in 56% of patients (42 actionable mutations and 24 rearrangements). These included BRAF alterations that directed the use of targeted inhibitors. Copy-number profiles differed across histologies. Combined Oncopanel and array-CGH identified subgroup specific alterations in 89% (17/19) of medulloblastomas. Rearrangement detection was aided by use of the combined assays including MYB-QKI, MYBL1, BRAF, FGFR3, and NTRK1 rearrangements. CONCLUSIONS: Oncopanel and array-CGH provide critical diagnostic, prognostic and treatment alterations. We demonstrate the feasibility of applying CLIA platforms as a precision medicine approach to identify driver genomic alterations in pediatric brain tumors.