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J Cancer Res Clin Oncol. 2007 Mar;133(3):185-92. Epub 2006 Oct 7.

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

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  • 1Department of Pediatric Surgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. mkaneko@md.tsukuba.ac.jp

Abstract

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.

PMID:
17028906
[PubMed - indexed for MEDLINE]
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