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  • Oncogenomics
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Expression profiling and characterization of 4200 genes cloned from primary neuroblastomas: identification of 305 genes differentially expressed between favorable and unfavorable subsets

Oncogene volume 22, pages 5525–5536 (2003)Cite this article

Abstract

Neuroblastoma (NBL), one of the most common childhood solid tumors, has a distinct nature in different prognostic subgroups: NBL in patients under 1 year of age usually regresses spontaneously, whereas that in patients over 1 year of age often grows aggressively and eventually kills the patient. To understand the molecular mechanism of biology and tumorigenesis of NBL, we decided to perform a comprehensive approach to unveil the gene expression profiles among the NBL subsets. We constructed the subset-specific oligo-capping cDNA libraries from the primary NBL tissues with favorable (F: stage 1, high expression of TrkA and a single copy of MYCN) and unfavorable (UF: stage 3 or 4, decreased expression of TrkA and MYCN amplification) characteristics and randomly cloned 4654 cDNAs. Among 4243 cDNAs sequenced successfully, 1799 (42.4%) were the genes with unknown function. Excluding the housekeeping genes, an expression profile of each subset was extremely different. To determine the genes expressed differentially between F and UF subsets, we performed semiquantitative reverse transcriptase (RT)–PCR for each of the 1842 independent genes using RNA obtained from 16 F and 16 UF NBLs as template. This revealed that 278 genes were highly expressed in the F subset as compared to the UF one, while, surprisingly, only 27 genes were expressed at higher levels in the UF rather than the F subset. These differentially expressed genes included 194 genes with unknown function. Many of the genes expressed at high levels in the F subset were related to catecholamine biosynthesis, small GTPases, synapse formation, synaptic vesicle transport, and transcription factors regulating differentiation of the neural crest-derived cells. On the other hand, the genes expressed at high levels in the UF subset included transcription factors and/or receptors that might regulate neuronal growth and differentiation. The chromosomal mapping of those genes showed some clusters. Thus, our mass-identification and characterization of the differentially expressed genes between the subsets may become a powerful tool for finding the important genes of NBL as well as developing new diagnostic and therapeutic strategies against aggressive NBL.

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Acknowledgements

We are grateful to the hospitals and institutions who provided us with the surgical specimens. We thank Shiho Hamano for helping with quantitative PCR analysis as well as statistical analysis, and Emiko Kojima, Natsue Kitabayashi, Hisae Murakami, Naoko Sugimitsu and Yuki Nakamura for technical support. We also appreciate helpful discussions with Masayuki Fukumura, Kenji Kadomastu, Minenobu Okayama and Hiroki Kurihara, and the encouragement given by Dr Naohiko Seki. This work was supported by a fund from Hisamitsu Pharmaceutical Company, and in part by a grant from grant-in-aid for Scientific Research on Priority Areas (C) ‘Medical Genome Science’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Division of Biochemistry, Chiba Cancer Center Research Institute, 666-2 Nitona, Chiba, 260-8717, Japan

    Miki Ohira, Aiko Morohashi, Hiroyuki Inuzuka, Tomotane Shishikura, Takemasa Kawamoto, Hajime Kageyama, Yohko Nakamura, Eriko Isogai, Hajime Takayasu, Shigeru Sakiyama & Akira Nakagawara

  2. Department of Cancer Virology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Yutaka Suzuki & Sumio Sugano

  3. Hisamitsu Co., Inc., 1-11-1 Marunouchi, Chiyoda-ku, Tokyo, 100-622, Japan

    Takeshi Goto & Shuji Sato

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  1. Miki Ohira
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Correspondence to Akira Nakagawara.

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Ohira, M., Morohashi, A., Inuzuka, H. et al. Expression profiling and characterization of 4200 genes cloned from primary neuroblastomas: identification of 305 genes differentially expressed between favorable and unfavorable subsets. Oncogene 22, 5525–5536 (2003). https://doi.org/10.1038/sj.onc.1206853

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