METB-01. EXTRACHROMOSOMAL DNA IS ASSOCIATED WITH ONCOGENE AMPLIFICATION AND POOR SURVIVAL ACROSS MULTIPLE PEDIATRIC CANCER TYPES

Circular extrachromosomal DNA (ecDNA) is an important driver of aggressive cancers. Its frequency and impact on the spectrum of 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 the association of ecDNA with survival using Kaplan Meier curves. In total, we analyzed a retrospective cohort of over 1600 tumor biopsies from 1400 different patients, spanning 69 different tumor types. We identified ecDNA in 14 tumor types. The incidence of ecDNA within these 14 tumors was 16% with the highest percentage in osteosarcoma (47%), pineoblastoma (40%) and rhabdomyosarcoma (40%). The overall incidence of ecDNA across the patient cohort was 10%. In analyzing matched diagnostic/relapse and relapse/progression pairs, ecDNA was noted to evolve over time with progression of disease. Across the cohort, ecDNA was found to be significantly associated with poor survival. Our preliminary results demonstrate that ecDNA is prevalent in pediatric cancer, can contain known and potentially novel oncogenes and can be associated with poorer outcomes across many different pediatric cancer types.