Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma
Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma
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DOI：
10.1158/1078-0432.ccr-05-2495
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发表时间：
2006-06-01
影响因子：
11.5
通讯作者：
Berthold, F
中科院分区：
文献类型：
--
作者：
Spitz, R;Hero, B;Berthold, F
目的：为了提高神经母细胞瘤的风险预测和指定可能复发的类型，分析了11号染色体长臂的改变。实验设计：使用间期荧光原位杂交研究了611例神经母细胞瘤远端11号染色体长臂的缺失事件。结果：在整个队列的611例肿瘤中，159例（26%）发现了11 q的改变，并且与4期疾病（P < 0.001）和诊断时年龄>2.5岁（P < 0.001）相关。在整个队列中，11 q缺失的患者的无事件生存率和总生存率明显较差（无事件生存期和总生存期，P < 0.001）和不同亚组：无MYCN扩增的神经母细胞瘤（MNA）（无事件生存期和总生存期，P < 0.001），使用MNA（无事件生存期，P = 0.03;总生存期，P = 0.02），以及MYCN非扩增1、2、3和4S期肿瘤伴和不伴del 1 p（无事件生存期和总生存期，P < 0.001）。在第4阶段，11 q状态没有区分结果。通过多变量分析，11 q状态被证明是整个队列（P = 0.008;风险比，1.573）和无MNA的1、2、3和4S期亚组（P < 0.001;风险比，3.534）无事件生存的预后因素。结论：11 q的改变不仅可以作为肿瘤复发的危险分层指标，还可以作为肿瘤复发的危险因素，特别是转移性肿瘤复发的危险因素。
Purpose: To improve risk prediction in neuroblastoma and to specify the type of a possible relapse, alterations in the long arm of chromosome 11 were analyzed.Experimental Design: A representative cohort of 611 neuroblastomas was investigated for deletion events in distal chromosome 11q using interphase fluorescence in situ hybridization.Results: Alterations in 11q were found in 159 of 611 tumors in the whole cohort (26%) and were associated with stage 4 disease (P < 0.001) and age at diagnosis of >2.5 years (P < 0.001). Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001). In stage 4, the 11q status did not discriminate outcome. By multivariate analysis, the 11q status proved prognostic for event-free survival in the whole cohort (P = 0.008; hazard ratio, 1.573) and in the subgroup of stages 1, 2, 3, and 4S without MNA (P < 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P < 0.001).Conclusion: In addition to the current risk stratification, the status of 11q enables the identification of patients with an increased risk for relapses in general and metastatic relapses in particular.