神经母细胞源性肿瘤患儿N-MYC基因拷贝数的变化及其临床意义

Copy number variations and its clinical significance of N-MYC gene in children with neuroblastic tumors

目的:研究N-MYC基因拷贝数在神经母细胞源性肿瘤(neuroblastic tumors,NTs)患者中的异常改变及其临床病理学意义。方法:收集483例NTs患儿肿瘤组织标本,其中包括神经母细胞瘤(neuroblastoma,NB)388例、节细胞神经母细胞瘤(ganglioneuroblastoma,GNB)89例、节细胞神经瘤(ganglioneuroma,GN)6例。运用荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测N-MYC基因拷贝数改变。考察N-MYC基因拷贝数改变与临床病理学特征的关系并进行生存分析。结果:483例NTs患儿N-MYC基因扩增率为12.4%。N-MYC基因扩增均发生在NB中,而在GNB及GN中未见其扩增(P<0.05)。N-MYC基因拷贝数改变更易发生在低分化程度的NB中(P=0.01),且随着分化程度降低,N-MYC基因扩增率增加。男性患儿N-MYC基因拷贝数改变的发生率多于女性患儿(P=0.05)。患儿年龄≤18个月者N-MYC基因扩增率有低于>18个月者的趋势(P=0.092)。生存分析显示:N-MYC基因扩增组患儿生存率明显低于获得组及正常组。结论:NTs患儿N-MYC基因扩增与NTs的类型、分化程度、性别、年龄及生存密切相关。本研究为NTs患者的诊断、治疗及预后提供可靠的参考和帮助。

Objective： To detect N-MYC gene copy number alterations, and to analyze their related clinicopathological implications in pediatric neuroblastic tumors（NTs）. Methods： A total of 483 NT samples were obtained, including 388 neuroblastomas（NBs）, 89 ganglioneuroblastomas（GNBs） and 6 ganglioneuromas（GNs）. Fluorescence in situ hybridization（FISH） was used to detect numerical aberrations of N-MYC. Statistical analysis was used to study its association with clinicopathological features, as well as with the survival rate of patients. Results： Of 483 NT cases, N-MYC amplification rate was 12.4%. Gene amplification of N-MYC were found only in NB, but not in any GNB or GN case（P〈0.05）. N-MYC gene amplification was more likely to occur in poorly differentiated neuroblastoma（P=0.01）, the rate of which was inversely related to tumor differentiation. The N-MYC amplification rate in male patients was higher than that in female patients（P=0.05）. There was a trend that the amplification rate of N-MYCgene was lower in patients ≤18 months as compared to patients 18 months, but difference was not significantly（P=0.092）. The univariate survival analysis showed that the survival rate of patients with N-MYC gene amplification was significantly lower than those with N-MYC gain or normal gene status. Conclusion： N-MYC gene amplification is tightly correlated with tumor type, differentiation, gender, age and survival. Detection of abnormal N-MYC copy number would be helpful for the diagnosis and prognosis of neuroblastic tumors.