Elsevier

Journal of Pediatric Surgery

Volume 41, Issue 12, December 2006, Pages 2032-2036
Journal of Pediatric Surgery

Single nucleotide polymorphism array analysis to predict clinical outcome in neuroblastoma patients☆,

https://doi.org/10.1016/j.jpedsurg.2006.08.002Get rights and content

Abstract

Purpose

Neuroblastoma (NB) is a heterogeneous tumor and demonstrates favorable or unfavorable outcomes. In Japan, a nationwide NB mass screening (MS) had been performed on 6-month-old infants for approximately 20 years, which might have detected almost all NB including regressing/maturing tumors. To clarify the heterogeneity of this tumor, we examined genetic alterations in the representative cases using genomewide microarrays.

Methods

Genomic DNA was extracted from 198 NB tissue samples and paired blood samples including 76 MS-detected cases and analyzed by single nucleotide polymorphism arrays.

Results

The single nucleotide polymorphism array classified the genetic aberrations into 4 types: whole gain/loss type, partial gain/loss type, MYCN-amplified type, and silent type. Most MS-detecting cases belonged to the whole gain/loss type, whereas unfavorable cases who died of disease showed partial gain/loss, MYCN-amplified, or silent types.

Conclusions

Genomewide genetic analysis is useful to predict the outcome of patients. Although the cases whose tumors showed whole gain/loss may respond well to contemporary therapy, sparing intensive surgery, current therapeutic strategy may be insufficient for the subgroups with partial gain/loss, MYCN-amplified, or silent type. Validation of these results would provide new tools to predict clinical outcome of children with NB.

Section snippets

Samples

In Japan, approximately 5000 children, including 2500 MS-detected children, were registered between 1981 and 2004 in a database maintained by the Japanese Society of Pediatric Surgeons [10]. In the present study, genomic DNAs were extracted from 198 NB samples including 76 MS-detected cases. Ages at diagnosis and stages at surgery according to the International Neuroblastoma Staging System (INSS) are shown in Table 1. All patients were diagnosed as having NB between 1991 and 1998 at the

Results

Good hybridization signal intensities were obtained, and genotype calls were obtained for more than 95% SNPs on all XbaI and HindIII microarrays. This confirms that the assay was performed correctly, and that no sample contamination occurred. The loci with allelic imbalance were determined for all chromosomes in each case. A case of whole chromosomal gain/loss was determined when SNP signals in each chromosome were gain (upward signals) or loss (downward signals). Such chromosomal aberrations

Discussion

Clinical, biologic, and genetic observations have clearly demonstrated that NB encompasses several different diseases [6], [7]. An Affymetrix platform to survey genomewide genetic alterations revealed that more than 4 subtypes exist in 1 disease entity of NB. And W-type tumor is rare in the elder patients but accounts for more than half of MS-detected tumors, including most of the regressing/maturing tumors. Because the outcome of the patients with W-type tumor is excellent regardless of stages

Acknowledgements

The authors acknowledge Ikuko Fukuba of N-BARD and Emi Fukuda of the Department of Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan, for technical assistance. We thank the Committees on Tumor Registration, Japanese Society of Pediatric Surgeons, and Japanese Society of Pediatric Oncology for providing the registered data or NB patients. And we also thank the research project for evaluating the efficacy of Japanese MS system in Health and Labour Science

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    • ☆

    This study was supported by a grant-in-aid for a scientific research (16-Kodomo-012) from the Ministry of Health, Labour, and Welfare of the Government of Japan.

    Presented at the 39th Annual Meeting of the Pacific Association of Pediatric Surgeons, May 14–18, 2006, Taipei, Taiwan.

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