Campbell Kevin, Gastier-Foster Julie M, Mann Meegan, Naranjo Arlene H, Van Ryn Collin, Bagatell Rochelle, Matthay Katherine K, London Wendy B, Irwin Meredith S, Shimada Hiroyuki, Granger M Meaghan, Hogarty Michael D, Park Julie R, DuBois Steven G
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts.
Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Cancer. 2017 Nov 1;123(21):4224-4235. doi: 10.1002/cncr.30873. Epub 2017 Jul 11.
High-level MYCN amplification (MNA) is associated with poor outcome and unfavorable clinical and biological features in patients with neuroblastoma. To the authors' knowledge, less is known regarding these associations in patients with low-level MYCN copy number increases.
In this retrospective study, the authors classified patients has having tumors with MYCN wild-type tumors, MYCN gain (2-4-fold increase in MYCN signal compared with the reference probe), or MNA (>4-fold increase). Tests of trend were used to investigate ordered associations between MYCN copy number category and features of interest. Log-rank tests and Cox models compared event-free survival and overall survival by subgroup.
Among 4672 patients, 3694 (79.1%) had MYCN wild-type tumors, 133 (2.8%) had MYCN gain, and 845 (18.1%) had MNA. For each clinical/biological feature, the percentage of patients with an unfavorable feature was lowest in the MYCN wild-type category, intermediate in the MYCN gain category, and highest in the MNA category (P<.0001), except for 11q aberration, for which the highest rates were in the MYCN gain category. Patients with MYCN gain had inferior event-free survival and overall survival compared with those with MYCN wild-type. Among patients with high-risk disease, MYCN gain was associated with the lowest response rate after chemotherapy. Patients with non-stage 4 disease (according to the International Neuroblastoma Staging System) and patients with non-high-risk disease with MYCN gain had a significantly increased risk for death, a finding confirmed on multivariable testing.
Increasing MYCN copy number is associated with an increasingly higher rate of unfavorable clinical/biological features, with 11q aberration being an exception. Patients with MYCN gain appear to have inferior outcomes, especially in otherwise more favorable groups. Cancer 2017;123:4224-4235. © 2017 American Cancer Society.
在神经母细胞瘤患者中，高水平MYCN扩增（MNA）与预后不良以及不良的临床和生物学特征相关。据作者所知，关于低水平MYCN拷贝数增加的患者中这些关联的了解较少。
在这项回顾性研究中，作者将患者分为患有MYCN野生型肿瘤、MYCN增益（与参考探针相比，MYCN信号增加2至4倍）或MNA（增加超过4倍）的肿瘤患者。趋势检验用于研究MYCN拷贝数类别与感兴趣特征之间的有序关联。对数秩检验和Cox模型比较了各亚组的无事件生存期和总生存期。
在4672例患者中，3694例（79.1%）患有MYCN野生型肿瘤，133例（2.8%）患有MYCN增益，845例（18.1%）患有MNA。对于每种临床/生物学特征，具有不良特征的患者百分比在MYCN野生型类别中最低，在MYCN增益类别中居中，在MNA类别中最高（P<0.0001），11q畸变除外，其发生率在MYCN增益类别中最高。与MYCN野生型患者相比，MYCN增益患者的无事件生存期和总生存期较差。在高危疾病患者中，MYCN增益与化疗后的缓解率最低相关。非4期疾病（根据国际神经母细胞瘤分期系统）患者和非高危疾病且MYCN增益患者的死亡风险显著增加，这一发现在多变量检验中得到证实。
MYCN拷贝数增加与不良临床/生物学特征的发生率越来越高相关，11q畸变除外。MYCN增益患者似乎预后较差，尤其是在其他方面更有利的组中。《癌症》2017年；123:4224 - 4235。©2017美国癌症协会。
