ecDNAs may spatially aggregate to form ecDNA hubs, permitting ecDNA–ecDNA interactions (Figs. 1c, left panel, 2d, right panel).17,18 ecDNAs within hubs exhibit higher levels of transcription compared to singleton ecDNAs within the same tumor cell.17 Such inter-ecDNA contacts likely occur through inter-molecular enhancer–promoter interaction bridged by BRD4, as demonstrated in the COLO320DM colon cancer cell line with MYC ecDNAs.17 However, the question of whether BRD4 is the universal ecDNA hub organizer warrants further investigation. This evidence concerns the gene BRD4 and malignant colon neoplasm.