Year 1 in the Molecular Era of Pediatric Brain Tumor Diagnosis: Application of Universal Clinical Targeted Sequencing in an Unselected Cohort of Children.

Purpose Next-generation sequencing is gaining acceptance as a clinical tool to aid diagnosis and guide treatment of pediatric cancer. Prior pilot studies have evaluated the feasibility and utility of clinical genomic profiling in a subset of selected patients with brain tumors. Here, we report an unselected prospective cohort study to evaluate the clinical use of universal targeted sequencing in pediatric patients with brain tumors. Methods We applied a universal sequencing protocol for all tumors of the CNS undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. All tumors were sequenced using the UW-OncoPlex platform, which is a multiplexed targeted deep gene sequencing panel that detects genetic alterations in 262 cancer-related genes performed in a College of American Pathologists-accredited Clinical Laboratory Improvements Amendments-certified laboratory. Results Eighty-eight patients underwent diagnostic evaluation during the study period, of which 85 tumors (95%) yielded sufficient DNA for sequencing, including 59 newly diagnosed and 26 relapsed. Clinically relevant genetic alterations were identified in 68 of 85 patients (80%). Of these, 57 (67%) had disease-defining or disease-modifying mutations, 44 (52%) had potentially targetable mutations, and 31 (36%) had mutations requiring germline follow-up. As of the last follow-up, seven patients had been prescribed targeted agents on the basis of sequencing results, and nine had confirmed deleterious germline mutations. Conclusion Clinically validated molecular profiling of pediatric brain tumors aids diagnosis and treatment of patients with a variety of high- and low-grade primary an d relapsed pediatric brain tumors. (C) 2018 by American Society of Clinical Oncology