Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc.

Abstract

Cellular oncogenes comprise a class of genes whose aberrant expression or function may be involved in the development of tumours. Indeed, several naturally occurring animal and human tumours are associated with consistent alterations in the structure or genomic position of particular cellular oncogenes. Recently, we isolated a DNA segment having limited similarity to c-myc (termed N-myc) from a human neuroblastoma cell line. Although N-myc was present as a single copy in normal cells, it was selectively amplified up to 140-fold in tumour cells from human neuroblastomas. Now, we have used somatic cell hybrids to show that N-myc is normally localized on the distal short arm of chromosome 2, and in situ hybridization to localize N-myc to chromosome 2p23-24. Further, in situ hybridization localizes amplified N-myc in neuroblastoma cells to homogeneously staining regions (HSRs) on different chromosomes. Thus, our results suggest that amplification and translocation of N-myc may be interrelated processes associated with human neuroblastoma, and demonstrate that the site of N-myc amplification is quite variable and bears no apparent relationship to either the normal single-copy locus or recognized sites of non-random chromosome alteration in human neuroblastoma.