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Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma

Authors

  • Junko Takita,

    1. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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    • J. Takita and M. Ishii contributed equally to this article.

  • Masami Ishii,

    1. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    2. Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
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    • J. Takita and M. Ishii contributed equally to this article.

  • Shuichi Tsutsumi,

    1. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    2. Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
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  • Yukichi Tanaka,

    1. Division of Pathology, Kanagawa Children's Medical Center, Kanagawa, Japan
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  • Keisuke Kato,

    1. Division of Pathology, Kanagawa Children's Medical Center, Kanagawa, Japan
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  • Yasunori Toyoda,

    1. Division of Hematology, Kanagawa Children's Medical Center, Kanagawa, Japan
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  • Ryoji Hanada,

    1. Division of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
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  • Keiko Yamamoto,

    1. Division of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan
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  • Yasuhide Hayashi,

    Corresponding author
    1. Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
    2. Gunma Children's Medical Center, Gunma, Japan
    • Gunma Children's Medical Center, 779 Shimohakoda, Kitatachibana, Gunma 377-8577, Japan
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  • Hiroyuki Aburatani

    Corresponding author
    1. Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
    • Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan
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Abstract

To investigate the various genetic characteristics of and differences between early- and advanced-stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two-way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these NB tumors. Although 9 of the 13 early-stage tumors (69%) and 4 of the 6 advanced-stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early- and advanced-stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of NB. These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real-time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early-stage group than in the advanced-stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early-stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB. © 2004 Wiley-Liss, Inc.

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