瘤内基因异质性和头癌复发
A S Pierik1, J B Poell1, A Brink1
1Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Otolaryngology/Head and Neck Surgery, Head and Neck Cancer Biology and Immunology laboratory, De Boelelaan 1117, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, De Boelelaan 1117, Amsterdam, the Netherlands.
概括
在化疗放射治疗 (CRT) 后,与基因无关的瘤复发是常见的. 瘤内基因异质性,而不是治疗引起的变化,可能解释了为什么复发瘤与原始瘤有不同的癌症驱动突变.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 癌症研究 癌症研究
背景情况:
- 在手术,放射治疗 (RT) 或化疗放射治疗 (CRT) 治疗后,头部和部状细胞癌经常在区域内复发.
- 在CRT治疗后,大约50%的局部区域复发 (LRs) 呈现与原发性瘤无关的癌症驱动突变.
- 这种差异需要对基因特异性复发的潜在原因进行调查.
研究的目的:
- 调查CRT后遗传无关LRs的两个潜在解释:治疗诱导的遗传变化和瘤内遗传异质性.
- 为了确定放射治疗或化学放射治疗是否诱导瘤中的克隆DNA变化.
- 为了评估手术治疗的头部和部瘤中瘤内遗传异质性的程度.
主要方法:
- 用 (C) RT.治疗的原发性和复发性异种移植瘤的拷贝数变化 (CNAs) 和突变的比较.
- 在11个手术治疗的瘤中从31个活检中采用了DNA的多区域测序,以研究瘤内异质性.
- 从单个瘤中建立了基因特异的异质细胞培养物,以分析生物标志物概况和药物敏感性.
主要成果:
- 在 (C) RT后的异种移植模型中没有观察到治疗诱导的克隆DNA变化的证据.
- 多区域测序揭示了个体瘤内CNA概况的显著变化,表明大量的副本数异质性.
- 在所有活检中确定了32种癌症驱动突变,但在11种瘤中的6种中也观察到这些驱动基因的多克隆突变. 从单个瘤中获得了具有不同药物敏感性的基因特异细胞培养.
结论:
- 瘤内基因异质性,特别是在癌症驱动突变水平上,是CRT后LR中观察到的异调突变特征的可能解释.
- 目前的异种移植模型没有提供CRT诱导这些遗传变化的证据.
- 了解瘤异质性对于解释治疗失败和指导头癌的未来治疗策略至关重要.
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