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Heterogeneous subgroups in human neuroblastoma for clinically relevant risk stratification

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Abstract

Neuroblastoma is a heterogeneous tumor and that may have a favorable or unfavorable prognosis. In Japan, a nation-wide neuroblastoma mass-screening (MS) project assessed 6-month-old infants between 1985 and 2003, and almost all neuroblastomas, including regressing or maturing tumors were thought to be detected in this period. To evaluate the heterogeneity of neuroblastoma subgroups, we analyzed patients with neuroblastoma who had been diagnosed during this period. The clinical courses of 4,209 patients with neuroblastoma, including 1,560 MS detected patients, whose tumors had been diagnosed between 1971 and 1995 were registered. The 2,520 cases registered between 1985 and 1995 were compared to 1,050 cases registered between 1971 and 1980 and analyzed by a multi-gene target model to determine the age distribution of neuroblastoma incidence. We hypothesized that three target genes were responsible for the progression of neuroblastoma: one pair of tumor suppressor gene alleles, one oncogene, and one gene controlling regression/differentiation. This simulation study revealed that the age distribution at initial diagnosis of neuroblastoma was divided into four groups based on post-fertilization age: 20–40, 40–50, 60–90, and 160–200 weeks. Since neuroblatoma in the first group occurred prenatal, post-natal clinical neuroblastoma can be classified into three age groups: 0–6 months, 1–2 years, and 3–4 years. The 0- to 6-month group consisted of mostly benign tumors, and the two older groups had predominantly malignant phenotypes. Our proposed model could explain qualitatively the distribution of neuroblastoma consisting of one subgroup with a favorable prognosis and two subgroups with unfavorable prognosis. For clinically relevant risk stratification, an age cutoff should be considered by the age distribution of these heterogeneous subgroups.

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Acknowledgments

This research was supported by Grant-in-Aid (16-Kodomo-IPPAN-012) from the Ministry of Health, Labour, and Welfare of Japan. We acknowledge Ikuko Fukuba, Yoko Chiba, Hitomi Ichikawa in N-BARD, Emi Fukuda in Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University for technical assistance. We thank the Committees on Tumor Registration, Japanese Society of Pediatric Surgeons and Japanese Society of Pediatric Oncology to providing the registered data or neuroblastoma patients. And we also thank members of the research project for evaluating the efficacy of Japanese mass-screening system in Health and Labour Science Research Grants for Research on Children and Families funded by Japanese Ministry of Health, Labour and Welfare to critical discussing of these data.

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Authors and Affiliations

  1. Natural Science Center for Basic Research and Development, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Eiso Hiyama & Masahiko Sugiyama

  2. Department of Pediatric Surgery, Hiroshima University, Hiroshima, Japan

    Eiso Hiyama & Hiroaki Yamaoka

  3. Research Group for Evaluating Japanese Mass-Screening project (H16-Kodomo-Ippan-012), Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan, Tokyo, Japan

    Eiso Hiyama, Hiroaki Yamaoka, Satoshi Kondo, Akihiro Yoneda, Tatsuro Tajiri, Masahiro Fukuzawa, Yutaka Hayashi, Fumiaki Sasaki & Megu Ohtaki

  4. Department of Surgery II, Nagoya City University, Nagoya, Japan

    Satoshi Kondo

  5. Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

    Akihiro Yoneda & Masahiro Fukuzawa

  6. Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    Tatsuro Tajiri

  7. Department of Pediatric Surgery, Tohoku University School of Medicine, Sendai, Japan

    Yutaka Hayashi

  8. Department of Pediatric Surgery, Tokyo University, Tokyo, Japan

    Masahiko Sugiyama

  9. Department of Pediatric Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Fumiaki Sasaki

  10. Department of Environmentrics and Biometrics, Hiroshima University Research Institute for Radiation Biology and Medicine, Hiroshima, Japan

    Megu Ohtaki

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  1. Eiso Hiyama
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  2. Hiroaki Yamaoka
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  3. Satoshi Kondo
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  4. Akihiro Yoneda
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  5. Tatsuro Tajiri
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  6. Masahiro Fukuzawa
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  7. Masahiko Sugiyama
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  8. Yutaka Hayashi
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  9. Fumiaki Sasaki
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  10. Megu Ohtaki
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Correspondence to Eiso Hiyama.

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Hiyama, E., Yamaoka, H., Kondo, S. et al. Heterogeneous subgroups in human neuroblastoma for clinically relevant risk stratification. Pediatr Surg Int 23, 1051–1058 (2007). https://doi.org/10.1007/s00383-007-1998-3

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  • DOI: https://doi.org/10.1007/s00383-007-1998-3

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