51. 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
- Author
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Nc, Cheng, Van Roy N, Chan A, Beitsma M, Westerveld A, Speleman F, Rogier Versteeg, and Other departments
- Subjects
Blotting, Southern ,Neuroblastoma ,Chromosomes, Human, Pair 1 ,Gene Amplification ,Genes, myc ,Tumor Cells, Cultured ,Chromosome Mapping ,Humans ,Genes, Tumor Suppressor ,Chromosome Deletion ,Hybrid Cells ,Blotting, Northern - 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.
- Published
- 1995