DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes.

DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes.
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DOI:
10.1038/nbt.2030
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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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体细胞拷贝数改变(SCNA)是许多癌症类型的标志,但其全基因组模式的机制基础仍然不完全清楚。在这里,我们整合了关于DNA复制时间,基因组物质之间的长程相互作用以及来自2,792个癌症样本的331,724个SCNA的数据,这些癌症样本被分为26种癌症类型。我们报告说,类似的复制时间的基因组区域在空间上聚集在细胞核中,SCNA的两个边界往往被发现在这样的地区,并复制早期和晚期显示不同的模式的频率SCNA边界,SCNA大小和插入的偏好删除。我们表明,远程相互作用和复制时间数据可以单独识别一个独立的测试数据集中的SCNA的显着比例。我们提出了一个在癌症中生成SCNA的模型,这表明同时复制的区域的空间接近性数据可用于预测癌症基因组的突变景观。
Somatic copy-number alterations (SCNA) are a hallmark of many cancer types, but the mechanistic basis underlying their genome-wide patterns remains incompletely understood. Here we integrate data on DNA replication timing, long-range interactions between genomic material, and 331,724 SCNAs from 2,792 cancer samples classified into 26 cancer types. We report that genomic regions of similar replication timing are clustered spatially in the nucleus, that the two boundaries of SCNAs tend to be found in such regions, and that regions replicated early and late display distinct patterns of frequencies of SCNA boundaries, SCNA size and a preference for deletions over insertions. We show that long-range interaction and replication timing data alone can identify a significant proportion of SCNAs in an independent test data set. We propose a model for the generation of SCNAs in cancer, suggesting that data on spatial proximity of regions replicating at the same time can be used to predict the mutational landscapes of cancer genomes.
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