Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma
Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma
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DOI：
10.1056/nejm199906243402504
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发表时间：
1999-06-24
影响因子：
158.5
通讯作者：
Speleman, F
中科院分区：
文献类型：
--
作者：
Bown, N;Cotterill, S;Speleman, F
背景染色体17 q臂遗传物质的获得（17 q21-qter片段的获得）是神经母细胞瘤细胞最常见的细胞遗传学异常。这种增加与晚期疾病、大于或等于1岁的患者、染色体臂1 p缺失和N-myc癌基因扩增相关，所有这些都预测不良结局。我们调查了这些相关性，并评估了17号染色体状态的预后重要性。方法我们对来自欧洲6个中心的313例原发性神经母细胞瘤患者进行了17号染色体的分子细胞遗传学分析。结果17 q21-qter异常增高者占53.7%，染色体正常者占46.3%。17 q的增加是晚期肿瘤和大于或等于1岁儿童肿瘤的特征，与1 p的缺失和N-myc的扩增密切相关。在1 p缺失或17 q增加的情况下，没有肿瘤显示N-myc扩增。在单因素分析中，17 q增加是不良结局的显著预测因素。在这种异常的患者中，5年总生存率为30.6%（95%置信区间为21%~ 40%），而17 q状态正常的患者为86.0%（95%置信区间为78%~ 91%）。在多因素分析中，17 q的获得是最有力的预后因素，其次是4期疾病和1 p缺失的存在（风险比，分别为3.4，2.3和1.9）。结论染色体片段17 q21-qter的获得是一个重要的预后因素，在儿童神经母细胞瘤。（N Engl J Med 1999;340：1954-61.）(C)1999年，马萨诸塞州医学会。
Background Gain of genetic material from chromosome arm 17q (gain of segment 17q21-qter) is the most frequent cytogenetic abnormality of neuroblastoma cells. This gain has been associated with advanced disease, patients who are greater than or equal to 1 year old, deletion of chromosome arm 1p, and amplification of the N-myc oncogene, all of which predict an adverse outcome. We investigated these associations and evaluated the prognostic importance of the status of chromosome 17.Methods We compiled molecular cytogenetic analyses of chromosome 17 in primary neuroblastomas in 313 patients at six European centers. Clinical and survival information were collected, along with data on 1p, N-myc, and ploidy.Results Unbalanced gain of segment 17q21-qter was found in 53.7 percent of the tumors, whereas the chromosome was normal in 46.3 percent. The gain of 17q was characteristic of advanced tumors and of tumors in children greater than or equal to 1 year of age and was strongly associated with the deletion of 1p and amplification of N-myc. No tumor showed amplification of N-myc in the absence of either deletion of 1p or gain of 17q. Gain of 17q was a significant predictive factor for adverse outcome in univariate analysis. Among the patients with this abnormality, overall survival at five years was 30.6 percent (95 percent confidence interval, 21 to 40 percent), as compared with 86.0 percent (95 percent confidence interval, 78 to 91 percent) among those with normal 17q status. In multivariate analysis, gain of 17q was the most powerful prognostic factor, followed by the presence of stage 4 disease and deletion of 1p (hazard ratios, 3.4, 2.3, and 1.9, respectively).Conclusions Gain of chromosome segment 17q21-qter is an important prognostic factor in children with neuroblastoma. (N Engl J Med 1999;340:1954-61.) (C) 1999, Massachusetts Medical Society.