In recent years, it has become apparent that extrachromosomal DNA (ecDNA) is a vehicle for oncogene amplification in most cancers and is associated with worse disease prognosis. What is necessary for ecDNA-positive tumors to develop is not yet fully clear. DNA breakage is a prerequisite for circularization, and we are currently mapping where the genome is likely to break and under which circumstances. In another project, we develop in vivo models of ecDNA-positive neuroblastoma to understand the conditions under which the creation of a single oncogene-carrying circular DNA molecule can lead to cancer.