肺癌和转移中的基因组转录组演变
Carlos Martínez-Ruiz1,2, James R M Black1,2, Clare Puttick1,2,3
1Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Nature
|April 12, 2023
概括
瘤内异质性驱动肺癌的发展和治疗耐药性. 这项研究揭示了转录组
科学领域:
- 癌症学
- 基因组学
- 转录组学
背景情况:
- 瘤内异质性 (ITH) 是肺癌进展,免疫逃避和治疗耐药性的关键驱动因素.
- 了解ITH的分子基础对于开发有效的肺癌治疗至关重要.
研究的目的:
- 研究非小细胞肺癌 (NSCLC) 中的内瘤转录组多样性.
- 探索基因表达,ITH和瘤进化之间的关系.
- 鉴定导致癌症进展和转移的基于RNA的机制.
主要方法:
- 354个NSCLC瘤和96个相邻的正常组织的TRACERx研究的整体外和RNA测序.
- 对947个瘤区域 (原发性和转移性) 的分析,以评估转录组变异.
- 机器学习的应用,将基因组和转录组数据与转移潜力联系起来.
主要成果:
- 转录组对NSCLC的表型变异和ITH有显著的贡献.
- 基因特异性表达,通常独立于副本数量的变化,与表观基因组功能障碍和基因组-转录基因组并行进化有关.
- 单基RNA替代特征涉及ADAR和APOBEC3A活动,显示正在进行的APOBEC活动.
- 转移潜力与突变的进化背景和原发性瘤的增多有关.
结论:
- 基因组和转录组之间的相互作用对塑造ITH和推动肺癌的演变至关重要.
- 转录组多样性和RNA编辑在肺癌进展和治疗耐药性方面发挥着重要作用.
- 基因组和转录组分析提供了对转移机制和潜在治疗点的见解.
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