非 MYCN 扩增二倍体神经母细胞瘤的片段染色体畸变数与诊断时年龄的相关性。

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

机构信息

Department of Pediatric Surgery, Kyushu University, Fukuoka, Japan.

出版信息

J Pediatr Surg. 2011 Dec;46(12):2228-32. doi: 10.1016/j.jpedsurg.2011.09.005.

DOI:10.1016/j.jpedsurg.2011.09.005

PMID:22152855

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.

摘要

背景

在无 MYCN 扩增的神经母细胞瘤（NB）中，已有人提出，片段染色体异常（如 1p 缺失、11q 缺失和 17q 增益）与患者的预后相关。我们评估了原发性 NB 样本中 SCAs 数量与其他生物学因素之间的相关性。

方法

使用单核苷酸多态性（SNP）阵列（Human CMV370-Duo；Illumina，圣地亚哥，CA）分析 54 个原发性 NB 样本中 SCAs 的状态。通过 SNP 阵列和荧光原位杂交法确定 MYCN 扩增状态。通过流式细胞术确定 DNA ploidy。

结果

9 个样本显示 MYCN 扩增。所有 9 个有 MYCN 扩增的样本和 45 个无 MYCN 扩增的样本中的 20 个均显示二倍体/四倍体，其余 25 个无 MYCN 扩增的样本显示非整倍体。最常见的 SCAs 是 17q 增益（26/54；48.1%）和 11q 缺失（16/54；29.6%），其次是 1p 缺失（15/54；27.8%）。无 MYCN 扩增的二倍体/四倍体 NB 中的 SCAs 数量（7.00±4.67）高于有 MYCN 扩增的 NB（4.78±2.82）和非整倍体 NB（1.64±2.78）（P<0.05）。在无 MYCN 扩增的二倍体/四倍体 NB 中，诊断时年龄小于 12 个月（n=7）与大于 12 个月（n=13）之间存在显著差异（4.14±3.63 vs 8.54±4.54；P=0.04）。此外，无 MYCN 扩增的二倍体/四倍体样本中，SCAs 数量与诊断时的年龄呈显著相关（r=0.70，P=0.0006）。在有 MYCN 扩增的 NB 中，SCAs 数量与诊断时的年龄无关。