High order chromatin architecture shapes the landscape of chromosomal alterations in cancer.

High order chromatin architecture shapes the landscape of chromosomal alterations in cancer.
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DOI:
10.1038/nbt.2049
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发表时间:
2011-11-20
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
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--
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癌症基因组结构信息的快速增长为更好地理解癌症基因组改变的突变机制和作用于它们的选择力提供了机会。在这里,我们测试两个主要力量的证据,空间染色体结构和净化(或负)选择,塑造了癌症中体细胞拷贝数改变(SCNAs)的景观。使用最大似然框架,我们比较SCNA地图和三维基因组结构确定的全基因组染色体构象捕获(HiC)和所提出的分形球(FG)模型。该分析提供了癌症中染色体改变的分布在空间上与三维基因组结构相关的证据,并且还表明纯化选择以及阳性选择在癌细胞的体细胞进化期间塑造了SCNA的景观。
The rapid growth of cancer genome structural information provides an opportunity for a better understanding of the mutational mechanisms of genomic alterations in cancer and the forces of selection that act upon them. Here we test the evidence for two major forces, spatial chromosome structure and purifying (or negative) selection, that shape the landscape of somatic copy-number alterations (SCNAs) in cancer. Using a maximum likelihood framework we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule (FG) model. This analysis provides evidence that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and additionally suggests that purifying selection as well as positive selection shapes the landscape of SCNAs during somatic evolution of cancer cells.
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