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

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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 ≥40 copies of MYCN (DDX1, p = 0.00058; NAG, p = 0.0242, χ2 for independence test). In patients with MYCN-amplified NB aged ≥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.

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Abbreviations

NB:

Neuroblastoma

DDX1 :

DEAD box polypeptide 1 gene

NAG :

Neuroblastoma-amplified gene

hnRNP K:

Heterogeneous nuclear ribonucleoprotein K

q-PCR:

Quantitative polymerase chain reaction

q-RT-PCR:

Quantitative reverse transcriptase/polymerase chain reaction

BCM :

B-cell maturation factor gene

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

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Authors and Affiliations

  1. Department of Pediatric Surgery, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan

    Setsuko Kaneko & Michio Kaneko

  2. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, 260-8717, Japan

    Miki Ohira, Yohko Nakamura, Eriko Isogai & Akira Nakagawara

Authors
  1. Setsuko Kaneko
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  2. Miki Ohira
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  3. Yohko Nakamura
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  4. Eriko Isogai
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  5. Akira Nakagawara
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  6. Michio Kaneko
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Correspondence to Setsuko Kaneko.

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Kaneko, S., Ohira, M., Nakamura, Y. et al. Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma. J Cancer Res Clin Oncol 133, 185–192 (2007). https://doi.org/10.1007/s00432-006-0156-y

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