Structural organization of MYCN amplicons of neuroblastoma tumors, xenografts, and cell lines characterized by the sequences encompassing the MYCN amplicons in a human neuroblastoma cell line

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Abstract
We characterized differences in the structural organization of the MYCN amplicons of a number of neuroblastomas by analyzing 8 contigs spanning 330 kb cloned from the MYCN amplicon of a neuroblastoma cell line. Some regions were amplified in almost all specimens, the conserved regions (CRs), and others were differentially amplified in some subsets, the non‐conserved regions (NCRs). CRs constituted only 20% of the 330 kb region, with the remainder being NCRs. The regions that inevitably co‐segregate with the MYCN gene make up the core, whereas flanking regions are retained at random. If a histogram of the frequency with which the amplified NCR sequences from one specimen match those of the cell line MC‐NB‐1 shows a random distribution, the NCRs would co‐segregate with MYCN as a result of random events. However, both the tumors and cell lines/xenografts showed a distribution with two distinct peaks; one from a group containing a small number of sequences with a fairly high degree of homology to the NCRs of MC‐NB‐1, and the other from a group containing a large number of sequences with little homology. These results indicate that the flanking segments are preferentially co‐segregated with MYCN by a non‐random mechanism.