Open adjacencies and k-breaks: detecting simultaneous rearrangements in cancer genomes.
Open adjacencies and k-breaks: detecting simultaneous rearrangements in cancer genomes.
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DOI：
10.1186/1471-2164-15-s6-s4
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发表时间：
2014
期刊：
影响因子：
4.4
通讯作者：
Raphael BJ
中科院分区：
文献类型：
--
作者：
Weinreb C;Oesper L;Raphael BJ
癌症基因组的演变传统上被描述为一段时间内突变的连续积累-包括染色体重排。然而，最近的研究表明，在一个单一的灾难性事件中，可能会同时获得许多重排，从而提出了新的重排机制，如chromothripsis和chromotherapy。我们引入了两种测量方法，开放邻接率（OAR）和拷贝数不对称富集（CAE），用于评估同时形成的断点（或k >2的k-断裂）与标准重排（或2-断裂）的顺序积累相比的患病率。我们将OAR和CAE应用于来自两项不同研究的121个癌症基因组的基因组测序数据。我们发现，OAR和CAE相关性以及与以前的分析chromothripsis/chromotherapy，但作出不同的预测基因组的一个小的子集。这些结果支持了同时重排的存在，但也表明了用不同的标准来表征这种重排的困难。
The evolution of a cancer genome has traditionally been described as a sequential accumulation of mutations - including chromosomal rearrangements - over a period of time. Recent research suggests, however, that numerous rearrangements may be acquired simultaneously during a single cataclysmic event, leading to the proposal of new mechanisms of rearrangement such as chromothripsis and chromoplexy. We introduce two measures, open adjacency rate (OAR) and copy-number asymmetry enrichment (CAE), that assess the prevalence of simultaneously formed breakpoints, or k-breaks with k >2, compared to the sequential accumulation of standard rearrangements, or 2-breaks. We apply the OAR and the CAE to genome sequencing data from 121 cancer genomes from two different studies. We find that the OAR and CAE correlate well with previous analyses of chromothripsis/chromoplexy but make differing predictions on a small subset of genomes. These results lend support to the existence of simultaneous rearrangements, but also demonstrate the difficulty of characterizing such rearrangements using different criterion.