title: 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.
abstract: 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.
authors.affiliation: Department of Child Health, Medical School, University of Newcastle upon Tyne, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: George
authors.forename: R M
authors.initials: RM
authors.lastname: Kenyon
authors.forename: A G
authors.initials: AG
authors.lastname: McGuckin
authors.forename: A J
authors.initials: AJ
authors.lastname: Malcolm
authors.forename: A D
authors.initials: AD
authors.lastname: Pearson
authors.forename: J
authors.initials: J
authors.lastname: Lunec
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D053487:DEAD-box RNA Helicases; D017931:DNA Primers; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007223:Infant; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases / Q000235:genetics*; D012264:Ribonucleotide Reductases / Q000235:genetics*; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D012264:Ribonucleotide Reductases; D012316:RNA Nucleotidyltransferases; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; D009955:Ornithine Decarboxylase