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Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature

Oncogene volume 27, pages 441–449 (2008)Cite this article

Abstract

Human neuroblastoma remains enigmatic because it often shows spontaneous regression and aggressive growth. The prognosis of advanced stage of sporadic neuroblastomas is still poor. Here, we investigated whether genomic and molecular signatures could categorize new therapeutic risk groups in primary neuroblastomas. We conducted microarray-based comparative genomic hybridization (array-CGH) with a DNA chip carrying 2464 BAC clones to examine genomic aberrations of 236 neuroblastomas and used in-house cDNA microarrays for gene-expression profiling. Array-CGH demonstrated three major genomic groups of chromosomal aberrations: silent (GGS), partial gains and/or losses (GGP) and whole gains and/or losses (GGW), which well corresponded with the patterns of chromosome 17 abnormalities. They were further classified into subgroups with different outcomes. In 112 sporadic neuroblastomas, MYCN amplification was frequent in GGS (22%) and GGP (53%) and caused serious outcomes in patients. Sporadic tumors with a single copy of MYCN showed the 5-year cumulative survival rates of 89% in GGS, 53% in GGP and 85% in GGW. Molecular signatures also segregated patients into the favorable and unfavorable prognosis groups (P=0.001). Both univariate and multivariate analyses revealed that genomic and molecular signatures were mutually independent, powerful prognostic indicators. Thus, combined genomic and molecular signatures may categorize novel risk groups and confer new clues for allowing tailored or even individualized medicine to patients with neuroblastoma.

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Acknowledgements

We thank institutions and hospitals for providing tumor specimens (see Supplementary Information). We also thank Shigeru Sakiyama, Hiroki Nagase, Iwao Nozawa, Tadayuki Koda and technical staff, past and present, at Division of Biochemistry, Chiba Cancer Center Research Institute. We acknowledge Hisamitsu Pharmaceutical Co. Inc., the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Ministry of Health, Labour and Welfare of Japan and the Hamaguchi Foundation for the Advancement of Biochemistry for funding this work.

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Author notes

  1. A Misra & B G Feuerstein

    Present address: 12Current address: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.,

  2. S Ishii

    Present address: 13Current address: Graduate School of Informatics, Kyoto University, Kyoto, Japan.,

  3. N Tomioka, S Oba and M Ohira: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, Japan

    N Tomioka, M Ohira, Y Nakamura, E Isogai & A Nakagawara

  2. Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, CA, USA

    N Tomioka, A Misra & B G Feuerstein

  3. Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

    N Tomioka & S Todo

  4. Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Japan

    S Oba & S Ishii

  5. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    J Fridlyand

  6. Hisamitsu Pharmaceutical Co. Inc., Tokyo, Japan

    T Hirata

  7. GENESHOT project, R&D Center, NGK Insulators, Ltd, Nagoya, Japan

    Y Yoshida

  8. Saitama Cancer Center Research Institute, Saitama, Japan

    Y Kaneko

  9. Department of Laboratory Medicine, University of California, San Francisco, CA, USA

    D G Albertson, D Pinkel & B G Feuerstein

  10. Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    D G Albertson, D Pinkel & B G Feuerstein

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  1. N Tomioka
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  2. S Oba
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Corresponding author

Correspondence to A Nakagawara.

Additional information

Supplementary Information accompanies the paper on the Oncogene web site (http://www.nature.com/onc).

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Tomioka, N., Oba, S., Ohira, M. et al. Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature. Oncogene 27, 441–449 (2008). https://doi.org/10.1038/sj.onc.1210661

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  • DOI: https://doi.org/10.1038/sj.onc.1210661

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