乳腺癌进展过程中多层次的3D基因组组织的丧失
Roberto Rossini1, Mohammadsaleh Oshaghi1, Maxim Nekrasov2
1Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, 0316 Oslo, Norway.
乳腺癌改变了三维 (3D) 基因组组织. 关键的变化包括隔间重组和新型MYC瘤基因插入,驱动恶性进展和基因激活.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 乳腺癌涉及复杂的基因组和基因表达变化.
- 三维 (3D) 染色质结构在乳腺癌进展中的作用尚不清楚.
研究的目的:
- 为了研究乳腺癌进展期间3D基因组组织的变化.
- 为了将结构性基因组变化与瘤基因表达相关联.
主要方法:
- 分析Hi-C数据,膜相关域 (LAD),表观遗传学标记和基因表达.
- 使用了乳腺癌进展的体外模型.
主要成果:
- 拓关联域 (TADs) 在很大程度上保持不变,但组件和子组件得到了显著的重组.
- 观察到TAD-TAD相互作用的重组和空间分区的丧失.
- 一种新的染色体间插入MYC瘤基因位点到染色体10导致了de novo增强器接触和MYC激活.
结论:
- 乳腺癌的进展与基因组组织的多层次损失有关.
- 结构性基因组变异可以通过改变3D基因组架构来驱动致癌状态.
- 揭示了3D基因组结构与乳腺癌中的瘤过程之间的新联系.
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