整个基因组的翻倍会导致染色体分离的致癌性损失
Ruxandra A Lambuta1,2, Luca Nanni2,3,4, Yuanlong Liu2,3,4
1Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, EPFL, Écublens, Switzerland.
Nature
|March 16, 2023
概括
全基因组倍增 (WGD) 在p53缺乏的癌细胞中导致染色体分离 (LCS) 的丧失. 这种由表观遗传变化驱动的染色体重组促进瘤基因激活和瘤进展,突出显示了WGD驱动的癌症中的染色体进化.
科学领域:
- 癌症生物学
- 基因组学
- 表观遗传学
背景情况:
- 全基因组倍增 (WGD) 在人类癌症中很常见,促进染色体不稳定性和动质积分.
- WGD对染色体3D组织的影响及其在癌症表型中的作用仍然基本不明.
研究的目的:
- 研究WGD癌细胞中的三维染色体组织.
- 确定WGD诱导的染色体变化对瘤原型的贡献.
主要方法:
- 在全基因组翻倍后对p53缺乏细胞的分析.
- 长度研究以追踪染色体组织的变化.
- 评估CTCF和H3K9me3在染色体分离中的作用.
主要成果:
- 在p53缺乏的细胞中,WGD诱导了染色体分离 (LCS) 的丧失,其特征是染色体大小和子区分的减少.
- 在绕过四体检查点的细胞中,LCS是由CTCF和H3K9me3水平的降低驱动的.
- 导致表观遗传和转录变化,从而激活瘤基因.
结论:
- 染色体分离的丧失是癌症中WGD的早期后果.
- 染色体重组独立于染色体变化,补充了推动瘤发展的遗传变化.
- 染色体进化是WGD驱动癌症的一个关键特征,影响瘤基因激活和进展.
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