Multiple amplicons of discrete sizes encompassing N-myc in neuroblastoma cells evolve through differential...

Human neuroblastoma cells often carry cytogenetic abnormalities signaling amplification of the gene N-myc. In most cell lines amplified N-myc is localized in homogeneously staining regions (HSRs). Varying proportions of the amplified DNA consist of multiple tandem arrays of DNA segments encompassing N-myc. Here we report the cloning and sequencing of a DNA breakpoint which represents the joint of the tandem repeats of a 280-kb amplicon of neuroblastoma line NMB. The breakpoint is located in the first intron of the N-myc gene and leads to the deletion of the 5' region of N-myc in this 20-copy amplicon. The representation of DNA derived from the non-N-myc part of the novel joint in the different amplicons suggests that an increase in N-myc copy numbers involves a multistep process proceeding from large 'precursors' to smaller multicopy amplicons.