L'Institut National de la Santé et de la Recherche Médicale U830, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
J Clin Oncol. 2010 Jul 1;28(19):3122-30. doi: 10.1200/JCO.2009.26.7955. Epub 2010 Jun 1.
Neuroblastoma is characterized by two distinct types of genetic profiles, consisting of either numerical or segmental chromosome alterations. The latter are associated with a higher risk of relapse, even when occurring together with numerical alterations. We explored the role of segmental alterations in tumor progression and the possibility of evolution from indolent to aggressive genomic types.
Array-based comparative genomic hybridization data of 394 neuroblastoma samples were analyzed and linked to clinical data.
Integration of ploidy and genomic data indicated that pseudotriploid tumors with mixed numerical and segmental profiles may be derived from pseudotriploid tumors with numerical alterations only. This was confirmed by the analysis of paired samples, at diagnosis and at relapse, as in tumors with a purely numerical profile at diagnosis additional segmental alterations at relapse were frequently observed. New segmental alterations at relapse were also seen in patients with segmental alterations at diagnosis. This was not linked to secondary effects of cytotoxic treatments since it occurred even in patients treated with surgery alone. A higher number of chromosome breakpoints were correlated with advanced age at diagnosis, advanced stage of disease, with a higher risk of relapse, and a poorer outcome.
These data provide further evidence of the role of segmental alterations, suggesting that tumor progression is linked to the accumulation of segmental alterations in neuroblastoma. This possibility of genomic evolution should be taken into account in treatment strategies of low- and intermediate-risk neuroblastoma and should warrant biologic reinvestigation at the time of relapse.
神经母细胞瘤的特征是两种不同类型的遗传特征，包括数字或片段染色体改变。后者与更高的复发风险相关，即使与数字改变同时发生也是如此。我们探讨了片段改变在肿瘤进展中的作用以及从惰性到侵袭性基因组类型演变的可能性。
对 394 个神经母细胞瘤样本的基于阵列的比较基因组杂交数据进行了分析，并与临床数据相关联。
整倍体和基因组数据的整合表明，具有混合数字和片段特征的假性三倍体肿瘤可能来源于仅具有数字改变的假性三倍体肿瘤。这通过对诊断时和复发时的配对样本的分析得到了证实，因为在诊断时具有纯数字谱的肿瘤中，在复发时经常观察到额外的片段改变。在诊断时具有片段改变的患者中也观察到新的片段改变。这与细胞毒性治疗的继发效应无关，因为即使在仅接受手术治疗的患者中也观察到了这种情况。更多的染色体断点与诊断时年龄较大、疾病分期较晚、复发风险较高以及预后较差相关。
这些数据进一步证明了片段改变的作用，表明肿瘤进展与神经母细胞瘤中片段改变的积累有关。在低危和中危神经母细胞瘤的治疗策略中应考虑到这种基因组进化的可能性，并应在复发时进行生物学再研究。
