Restriction fragment length polymorphisms of the human N-myc gene: relationship to gene amplification.

Using Southern blot hybridization with N-myc probes, we observed two restriction fragment length polymorphisms (RFLPs) in the Japanese population. One of the RFLPs was accounted for by the presence (allele S1) or absence (S2) of a SphI site in the second intron of the N-myc gene, and the other was explained by the presence (P1) or absence (P2) of a PvuII site in the 3' region of the gene. The allele frequencies of P1 and P2 were not significantly differently between the normal population and neuroblastoma patients with the minor allele frequency being 38-40% for P2. Frequencies of the S1 allele were 28% and 24% in neuroblastoma patients and the normal population, respectively. Fewer S1S1 homozygotes and more S1S2 heterozygotes than expected were observed in the normal population. No individuals with the S1P2 haplotype were observed due to an extreme linkage disequilibrium between the two RFLP loci. Amplification of N-myc in embryonal tumors was random with respect to the P allele, and strictly associated with the S2 allele in six cases of fresh tumors and three cases of cultured cell lines.