Elsevier

Journal of Pediatric Surgery

Volume 46, Issue 12, December 2011, Pages 2228-2232
Journal of Pediatric Surgery

PAPS paper
Correlation between the number of segmental chromosome aberrations and the age at diagnosis of diploid neuroblastomas without MYCN amplification

https://doi.org/10.1016/j.jpedsurg.2011.09.005Get rights and content

Abstract

Background

In neuroblastomas (NBs) without MYCN amplification, segmental chromosome aberrations SCAs such as 1p loss, 11q loss, and 17q gain have been suggested to be associated with the prognosis of the patients. We assessed the correlation between the number of SCAs and other biological factors in primary NBs samples.

Method

The status of SCAs in 54 primary NBs samples was analyzed using the single-nucleotide polymorphism (SNP) array (Human CMV370-Duo; Illumina, San Diego, CA). The status of MYCN amplification was determined by an SNP array and the fluorescence in situ hybridization method. The DNA ploidy was determined by flow cytometry.

Results

Nine of 54 samples showed MYCN amplification. All 9 samples with MYCN amplification and 20 of 45 samples without MYCN amplification showed diploidy/tetraploidy, and the other 25 samples without MYCN amplification showed aneuploidy. The most frequent SCAs were 17q gain (26/54; 48.1%) and 11q loss (16/54; 29.6%), followed by 1p loss (15/54; 27.8%). The number of SCAs in diploidy/tetraploidy NBs without MYCN amplification (7.00 ± 4.67) was higher than that in NBs with MYCN amplification (4.78 ± 2.82) and in aneuploid NBs (1.64 ± 2.78) (P < .05). In diploid/tetraploid NBs without MYCN amplification, there was a significant difference between an age at diagnosis less than 12 months (n = 7) and over 12 months (n = 13) (4.14 ± 3.63 vs 8.54 ± 4.54; P = .04). Moreover, the number of SCAs correlated with the age at diagnosis in diploid/tetraploid samples without MYCN amplification (r = 0.70, P = .0006). In NBs with MYCN amplification, the number of SCAs did not correlate with the age at diagnosis.

Conclusion

The number of SCAs significantly increased in proportion to age at diagnosis in diploid/tetraploid NBs without MYCN amplification. The increase in the number of these SCAs may play an important role in the prognosis of patients without MYCN amplification over 12 months of age.

Section snippets

Patient clinical data and biological data of NB samples

Patients with NB, evaluated in the Department of Pediatric Surgery in Kyushu University, were diagnosed between April 1988 and March 2008. The tumors were staged according to the International Neuroblastoma Staging System (INSS). All of the parents of the patients provided their informed consent for tumor preservation and the biological analysis before surgery. We have obtained the comprehensive agreement for all samples. This study was performed according to ethical guidelines for clinical

SCAs and MYCN gene amplifications

Nine of 54 samples showed MYCN amplification. All 9 samples with MYCN amplification (group 1) and 20 of 45 samples without MYCN amplification showed diploidy/tetraploidy (group 2), and other 25 samples without MYCN amplification showed aneuploidy (group 3). One or more SCAs were detected in 37 (68.5%) of all 54 samples. In all 54 samples, the most frequently observed SCAs were 17q gain (26/54; 48.1%) and 11q loss (16/54; 29.6%), followed by 1p loss (15/54; 27.8%) (Table 2). The 1p loss and 17q

Discussion

In the present study, the number of SCAs such as 11q loss, 17q gain, and 1p loss, significantly increased in proportion to the age at diagnosis in patients with diploid/tetraploid NBs without MYCN amplification. Spitz et al [13] previously reported that 11q and 3p loss were also associated with advanced stage disease and that the children with 11q deletion and 3p deletion were older than those with normal 11q and normal 3q loss. 17q gain was reported to be associated with factors related to a

Acknowledgments

The authors thank Dr. Ken Yamamoto for helpful discussions and thank Brian Quinn for reading and editing the manuscript.

References (15)

There are more references available in the full text version of this article.

Cited by (4)

  • Neuroblastoma

    2013, Cancer Genomics: From Bench to Personalized Medicine
  • Neuroblastoma in adults: Diagnosis and treatment

    2014, Chinese Journal of Clinical Oncology

Presented at the Pacific Association of Pediatric Surgeons 44th Annual Meeting, Cancun, Mexico, April 10-14, 2011.

View full text