AMPLIFICATION OF ONCOGENE N-MYC AND THE ADJACENT DNA FRAGMENTS IN HUMAN NEUROBLASTOMA: COMPARISON IN PRIMARY AND METASTASIZED TUMORS AND IN THE ESTABLISHED CELL LINE

Amplification of oncogene N-myc and the adjacent DNA fragments, clone 8 and G21 was observed in the primary neuroblastoma from a female patient at stage III and in the metastatic tumors from the same patient. The three DNA loci were amplified to the same degree in all tumor specimens, including an established cell line (SCMC-N3) of the primary tumor. Neither visible double minutes (DMs) nor homogeneously staining regions (HSRs) were recognized in the primary tumor by light microscope. However, numerous DMs were found in the established cell line with elevated N-myc expression, and in situ hybridization showed them to be the site of amplification for the N-myc, clone 8 and G21. These results suggest that the DNA amplification occurred in the primary tumor prior to metastasis and, probably, in the small DMs or precursors of DMs which were undetactable by light microscope.