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大规模的拓变化抑制了结肠直肠癌的恶性进展
Sarah E Johnstone1, Alejandro Reyes2, Yifeng Qi3
1Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Cell
|August 26, 2020
概括
癌症改变了基因组结构, 破坏了开放和封闭的空间分区. 这些拓变化可能会抑制瘤生长,抑制茎和侵袭,同时诱导抗瘤免疫力.
科学领域:
- 基因组学
- 癌症生物学
- 表观遗传学
背景情况:
- 癌症与广泛的DNA甲基化和染色质变化有关.
- 这些改变对更高层次染色体结构的影响尚不清楚.
研究的目的:
- 在结肠瘤中表征染色体循环,拓相关域和大规模基因组组的变化.
- 研究这些拓变化对癌症进展的功能后果.
主要方法:
- 结合结肠瘤和正常结肠的拓图.
- 对表观遗传,转录和成像数据的分析.
- 恶性和非恶性细胞中的基因组组织比较.
主要成果:
- 在瘤中,开放和关闭基因组的空间分区被显著破坏.
- 与瘤相关的拓变化包括分区特定的低甲基化和染色质变化.
- 在瘤中重新组织了A/B区间接口的新区间,在过度分裂的非恶性细胞中观察到类似的变化.
结论:
- 瘤相关的拓基因组变化可能会抑制干和入侵程序.
- 这些变化可以诱导抗瘤免疫基因,可能抑制恶性进展.
- 这些发现挑战了癌症表观基因变化仅仅是癌症.
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