Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group

Oncogene. 1996 Apr 4;12(7):1583-7.


Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases
  • DNA Primers
  • Gene Amplification
  • Genes, myc*
  • Humans
  • Infant
  • Membrane Glycoproteins / genetics*
  • Molecular Sequence Data
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Ornithine Decarboxylase / genetics*
  • Proteoglycans / genetics*
  • RNA Helicases*
  • RNA Nucleotidyltransferases / genetics*
  • Ribonucleotide Reductases / genetics*
  • Syndecan-1
  • Syndecans
  • Tumor Cells, Cultured


  • DNA Primers
  • Membrane Glycoproteins
  • Proteoglycans
  • SDC1 protein, human
  • Syndecan-1
  • Syndecans
  • Ribonucleotide Reductases
  • RNA Nucleotidyltransferases
  • DDX1 protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases
  • Ornithine Decarboxylase