Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS tumour and its cell line.

Amplification of the MYCN gene is frequently seen either in extrachromosomal double minutes (DMs) or in homogeneously staining regions (HSRs) of aggressively growing neuroblastomas. Total genomic DNA from cell line LS, from early passages of the same line and from original tumour material was biotinylated and hybridised to metaphase chromosomes of normal human lymphocytes. The reverse genomic hybridisation revealed the amplified DNA to be derived both from chromosome 2p23-24, which is the position of MYCN, and from chromosome 12 band q13-14. The MDM2 gene, located at 12q13-14, was found amplified both in early and late passages of LS, in addition to amplified MYCN. Amplification units of MYCN and MDM2 appear first to develop within DMs, which then integrate into different chromosomes to develop to HSRs.