While the first possibility is plausible, emerging evidence suggests that the ecDNA structure is unstable and is shaped throughout the disease progression, whose structural complexity may increase alongside.7,53 The use of parallel sequencing of extrachromosomal circular DNA and transcriptome at single-cell resolution (scEC&T-seq) allows us to infer the dynamics of ecDNA evolution.53 For example, in a neuroblastoma patient sample, many MYCN ecDNA subspecies were found in different clones. The gene discussed is MYCN; the disease is neuroblastoma.