Epco-45. Extrachromosomal Dna Promotes Oncogene Amplification Across Multiple Pediatric Cancer Types

Abstract

Extrachromosomal circular DNA (ecDNA) is an important driver of aggressive cancers. Its frequency and impact on pediatric cancers has yet to be fully described. To determine the ecDNA prevalence in various pediatric cancer types, we accessed whole genome sequencing (WGS) data in the Children’s Brain Tumor Network (CBTN) and St. Jude cancer cloud genomics platforms and utilized the bioinformatics tools Amplicon Architect (AA) and Amplicon Classifier (AC) to reconstruct ecDNA sequence structures. We then identified which genes were amplified on the ecDNA and how ecDNA correlated with survival, using Kaplan Meier curves. Different cancer types were noted to have varying prevalence of ecDNA with the highest detection in pediatric high-grade gliomas (30% of cases). In analyzing matched diagnostic/relapse and relapse/progression pairs, ecDNA was noted to evolve over time with progression of disease. Our preliminary results demonstrate that ecDNA is prevalent in pediatric cancer, can contain known and potential novel oncogenes and can be associated with poorer outcomes across many different pediatric cancer types.