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Open adjacencies and k -breaks: detecting simultaneous rearrangements in cancer genomes

机译:公开毗邻和k次κBreak:检测癌症基因组的同时重排

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Background 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. Results 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. Conclusions 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.
机译:背景技术癌症基因组的演变传统上被描述为突变的顺序积累 - 包括染色体重排 - 在一段时间内。然而,最近的研究表明,在单个灾难性的事件中可以同时获取许多重排,导致诸如Chromothripsis和Chromoplexy等新的重排机制的提议。结果我们介绍了两种措施,开放邻接率(OAR)和复制数不对称富集(CAE),其评估与标准重排的顺序积累相比,评估同时形成的断裂点,或k-2的k-breakbreaks的患病率,或者2-休息。我们将OAR和CAE应用于来自两种不同研究的121个癌症基因组的基因组测序数据。结论我们发现OAR和CAE与先前的Chromothripsis / Chromolexy分析相关,但对基因组的小子集进行了不同的预测。这些结果支持对同时重排的存在,但也展示了使用不同标准表征这种重排的难度。

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