A. EcDNA complex structures across different cancer types. EcDNA molecules can differ in sizes, oncogenes and segment composition. Schematic structures of a single-interval amplicon in leukemia (Left, PMID: 29467491), a rearranged amplicon in lung cancer with single chromosome origination (Middle, PMID: 32873787) and an amplicon in glioblastoma with segments from multiple chromosomes (Right, PMID: 29686388) are shown. B. EcDNA biogenesis, plasticity and evolution. EcDNA can be formed in multiple nonexclusive processes including chromothripsis, episome model, breakage-fusion-bridge (BFB) cycles, and translocation-excision-deletion-amplification (TEDA). Selection pressure may result in copy number changes and structure alterations of ecDNA as well as switch between ecDNAs and HSRs.