DELETION MAPPING IN NEUROBLASTOMA CELL-LINES SUGGESTS 2 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 chromo some 1 (1p) and amplification of the N-myc oncogene, We have made soma tic cell hybrids of two human neuroblastoma cell lines, one with and o ne without N-myc expression and amplification, The expression of the a mplified N-myc gene is completely switched off in the hybrids, This su ggests that N-myc expression results from loss of a repressor function , As N-myc amplification is associated with loss of heterozygosity (LO H) of 1p36, we analysed 1p deletions in 16 neuroblastoma cell lines, T he seven cell lines without N-myc amplification have no deletions or r elatively small deletions, with an SRO on 1p36.23-33. This suggests th at a tumor suppressor gene maps in this region, All nine cell lines wi th 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, Fin e mapping of 1p36 deletions in the two cell lines of the fusion experi ment suggests that the distal locus is not a repressor of N-myc expres sion, but the more proximal locus could be a candidate for this functi on.