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.
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-I 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-I, 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.
Akiyama
K
K
Life Science Research Laboratory, Japan Tobacco, Inc., Kanagawa.
Kanda
N
N
Yamada
M
M
Kato
M
M
Tadokoro
K
K
Matsunaga
T
T
Nishi
Y
Y
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D005784:Gene Amplification; D015321:Gene Rearrangement; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured