Deletion mapping in neuroblastoma cell lines suggests two distinct tumor suppressor genes in the 1p35-36 region, only one of which is associated with N-myc amplification

Oncogene. 1995 Jan 19;10(2):291-7.

Abstract

Neuroblastoma is characterized by deletions of the short arm of chromosome 1 (1p) and amplification of the N-myc oncogene. We have made somatic cell hybrids of two human neuroblastoma cell lines, one with and one without N-myc expression and amplification. The expression of the amplified N-myc gene is completely switched off in the hybrids. This suggests that N-myc expression results from loss of a repressor function. As N-myc amplification is associated with loss of heterozygosity (LOH) of 1p36, we analysed 1p deletions in 16 neuroblastoma cell lines. The seven cell lines without N-myc amplification have no deletions or relatively small deletions, with an SRO on 1p36.23-33. This suggests that a tumor suppressor gene maps in this region. All nine cell lines with N-myc amplification have larger deletions, with an SRO from 1p35-36.1 to the telomere. This suggests that a second tumor suppressor gene which is associated with N-myc amplification maps more proximally. Fine mapping of 1p36 deletions in the two cell lines of the fusion experiment suggests that the distal locus is not a repressor of N-myc expression, but the more proximal locus could be a candidate for this function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Blotting, Southern
  • Chromosome Deletion*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1*
  • Gene Amplification
  • Genes, Tumor Suppressor*
  • Genes, myc*
  • Humans
  • Hybrid Cells
  • Neuroblastoma / genetics*
  • Tumor Cells, Cultured