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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma
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High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma

机译：Myc通路活性高和神经元分化低下与神经母细胞瘤预后不良有关

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摘要

The childhood cancer neuroblastoma arises in the developing sympathetic nervous system and is a genotypically and phenotyp-ically heterogeneous disease. Prognostic markers of poor survival probability include amplification of the MYCN oncogene and an undifferentiated morphology. Whereas these features discriminate high- from low-risk patients with precision, identification of poor outcome low- and intermediate-risk patients is more challenging. In this study, we analyze two large neuroblastoma mi-croarray datasets using a priori-defined gene expression signatures. We show that differential overexpression of Myc transcriptional targets and low expression of genes involved in sympathetic neuronal differentiation predicts relapse and death from disease. This was evident not only for high-risk patients but was also robust in identifying groups of poor prognosis patients who were otherwise judged to be at low- or intermediate-risk for adverse outcome. These data suggest that pathway-specific gene expression profiling might be useful in the clinic to adjust treatment strategies for children with neuroblastoma.
机译：儿童癌症神经母细胞瘤出现在发展中的交感神经系统中，是一种基因型和表型异质性疾病。存活率低的预后标志物包括MYCN癌基因的扩增和形态未分化。尽管这些功能可以准确地区分高危患者与低危患者，但是识别不良预后的低危患者和中危患者则更具挑战性。在这项研究中，我们使用先验定义的基因表达特征分析了两个大型神经母细胞瘤微阵列数据集。我们表明，Myc转录目标的差异过表达和参与交感神经元分化的基因的低表达预测疾病的复发和死亡。这不仅对于高风险患者而言很明显，而且在确定预后差的患者组方面也很有效，否则这些患者被认为处于不良后果的低风险或中等风险。这些数据表明，通路特异性基因表达谱分析可能在临床上可用于调整神经母细胞瘤患儿的治疗策略。

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