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 either in extrachromosomal double minutes or in homogeneously staining regions of aggressively growing neuroblastomas. N-MYC maps to chromosome 2 band p23-24, but homogeneously staining regions have never been observed at this band, suggesting transposition of N-MYC during amplification. Previous studies had suggested that in cells with amplified N-MYC 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 fluorescence in situ hybridization, that N-MYC is occasionally duplicated at its resident site in neuroblastoma cell lines previously thought to 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 becomes activated.
Corvi
R
R
Division of Cytogenetics-0130, Deutsches Krebsforschungszentrum, German Cancer Research Center, Heidelberg.
Savelyeva
L
L
Schwab
M
M
D002889:Chromosomes, Human, Pair 2; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D005810:Multigene Family; D009447:Neuroblastoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D014407:Tumor Cells, Cultured