Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome

摘要: Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis. However, recent studies have shown that the mutational burden increases relapse, likely as result clonal evolution mutation-carrying cells during primary treatment. To inform development personalized therapies, we sought to further define frequency potentially actionable in neuroblastoma, both diagnosis and after chemotherapy. We performed retrospective study determine mutation frequency, only inclusion criterion being availability cancer gene panel sequencing data from Foundation Medicine. analyzed 151 neuroblastoma tumor samples: 44 obtained diagnosis, 42 second look surgery or biopsy for stable disease chemotherapy, 59 relapse (6 were unknown time points). Nine patients had multiple biopsies. ALK was most commonly mutated this cohort, observed higher suspected oncogenic relapsed than Patients with had, on average, greater number reported be cancer, genes are targetable available therapeutics. also an enrichment RAS/MAPK pathway tumors Our support evidence suggesting neuroblastomas undergo substantial therapy, more driven pathway, highlighting it critical base treatment decisions molecular profile will necessary conduct prospective clinical trials match results targeted therapeutic intervention if genomic profiling improves patient outcomes.