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.
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.
Department of Human Genetics, University of Amsterdam, Academic Medical Centre, The Netherlands.
N C
NC
Cheng
N
N
Van Roy
A
A
Chan
M
M
Beitsma
A
A
Westerveld
F
F
Speleman
R
R
Versteeg
D015152:Blotting, Northern; D015139:Blotting, Southern; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006801:Humans; D006822:Hybrid Cells; D009447:Neuroblastoma / Q000235:genetics*; D014407:Tumor Cells, Cultured