The NRAS amplicon breakpoints coincided with boundaries of topologically associating domains in a melanoma cell line (Extended Data Fig. 3e); the 3′ portion of the amplicon region encompasses a topologically associating domain containing multiple peaks of histone H3 lysine 27 acetylation (H3K27ac) in at least one of seven human cell types (Extended Data Fig. 3e,f), pointing to potential enhancers that may be rewired to the 5′ located NRAS gene via ecDNA circularization. Here, NRAS is linked to melanoma.