DUPLICATION OF N-MYC AT ITS RESIDENT SITE 2P24 MAY BE A MECHANISM OF ACTIVATION ALTERNATIVE TO AMPLIFICATION IN HUMAN NEUROBLASTOMA-CELLS

Amplification of the human N-MYC proto-oncogene is frequently seen eit her in extrachromosomal double minutes or in homogeneously staining re gions of aggressively growing neuroblastomas. N-MYC maps to chromosome 2 band p23-24, but homogeneously staining regions have never been obs erved at this band, suggesting transposition of N-MYC during amplifica tion. Previous studies had suggested that in cells with amplified N-MY C the chromosomes 2 appear to be unaltered and to carry one apparently normal copy of N-MYC each. In contrast, the contribution of N-MYC to tumors which lack amplification has been unclear. We here show, by flu orescence in situ hybridization, that N-MYC is occasionally duplicated at its resident site in neuroblastoma cell lines previously thought t o have a single copy gene. Additionally, we detected duplication in a neuroblastoma cell line carrying amplification. Our results raise the possibility that duplication may, in some neuroblastomas, either be a prelude to amplification or an alternative pathway by which N-MYC beco mes activated.