与神经母细胞瘤高风险临床过程相关的分子特征最初被诊断为非高风险的神经母细胞瘤
Rixt S Bruinsma1, Wendy W J de Leng2, Marta F Fiocco1,3,4
1Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Cancers
|January 28, 2026
概括
分段染色体异常 (SCAs) 和1p删除识别了神经母细胞瘤患者具有高风险的临床过程. 这些分子标记物,以及ALT激活和特定基因放大,预测非高风险神经母细胞瘤的不良结果.
科学领域:
- 儿科瘤学 儿科瘤学
- 癌症基因组学 癌症基因组学
- 分子病理学分子病理学
背景情况:
- 一些最初被归类为非高风险的神经母细胞瘤患者表现出侵袭性疾病和糟糕的生存率.
- 识别分子驱动因素对于理解这种差异至关重要.
研究的目的:
- 在诊断时识别出在非高风险神经母细胞瘤患者中预测高风险临床过程的分子异常.
- 研究细分染色体异常 (SCAs) 和端粒维护机制 (TMM) 的作用.
主要方法:
- 在89名非高风险神经母细胞瘤患者的SCAs,基因放大,突变和TMM的分析,这些患者在2014-2021年期间被诊断为高风险神经母细胞瘤.
- 使用单核酸多态阵列,下一代测序和FISH,WGS,RNA测序.
- 对于SCA计数,使用了多重归算.
主要成果:
- 在患有高风险病程的患者中,SCA 概况 (≥1 SCA) 显著更频繁 (76% vs 15%,p=0.004).
- 1p删除 (p=0.034),1q,2p,17q的增加,4p,11q的删除和更高的SCA数量与高风险的结果有关.
- 在57%的高风险患者中激活了替代端粒延长 (ALT),在两个病例中观察到MDM2/CDK4放大.
结论:
- SCA 概况和1p 删除是神经母细胞瘤高风险临床过程的显著预测因素.
- 作为风险分层的潜在生物标志物,ALT激活,MDM2/CDK4联合放大和特定的SCAs需要进一步调查.
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