Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma

J Cancer Res Clin Oncol. 2007 Mar;133(3):185-92. doi: 10.1007/s00432-006-0156-y. Epub 2006 Oct 7.


Purpose: Amplification of the MYCN gene strongly correlates with advanced stage, rapid tumor progression and poor prognosis in neuroblastoma (NB). Several genes in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and neuroblastoma-amplified gene (NAG gene), have been found to be frequently co-amplified with MYCN in NB. The aim of this study was to clarify the prognostic significance of the co-amplification or overexpression of DDX1 and NAG with MYCN.

Procedure: The gene copy numbers and mRNA expression levels of MYCN, DDX1, and NAG in 113 primary NBs were determined by the real-time quantitative polymerase chain reaction or quantitative reverse transcriptase/polymerase chain reaction assay. The relationships between gene co-amplification/overexpression status and stage, age at diagnosis, and overall survival were analyzed.

Results: For evaluating the frequency of DDX1 and NAG co-amplification, it proved appropriate to discriminate NBs with <40 copies of MYCN amplification from those with > or =40 copies of MYCN (DDX1, p = 0.00058; NAG, p = 0.0242, chi(2) for independence test). In patients with MYCN-amplified NB aged > or =18 months, those with tumor with enhanced DDX1 expression and low-NAG expression showed a significantly better outcome than those with low-DDX1 expression or enhanced NAG expression (p = 0.0245, log-rank test). None of the gene expression statuses had a significant relation to disease stage or survival for patients <18 months old. No relationship between any gene co-amplification status and disease stage, age at diagnosis, or overall survival was found.

Conclusions: Our findings suggest that there may be a subset of NB in which enhanced DDX1 and low-NAG expression consequent to DDX1 co-amplification without NAG amplification contributes to susceptibility to intensive therapy. A larger study using an age cut-off of 18 months will be required.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases / genetics*
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Gene Amplification / genetics*
  • Gene Dosage / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, myc / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Neoplasm Proteins / genetics*
  • Neuroblastoma / genetics*
  • Neuroblastoma / mortality
  • Neuroblastoma / therapy
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Survival Analysis
  • Survival Rate
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • NBAS protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • DDX1 protein, human
  • DEAD-box RNA Helicases