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Processes shaping cancer genomes – From mitotic defects to chromosomal rearrangements
DNA Repair ( IF 3.0 ) Pub Date : 2021-08-10 , DOI: 10.1016/j.dnarep.2021.103207
Kristina Keuper 1 , Angela Wieland 1 , Markus Räschle 1 , Zuzana Storchova 1
Affiliation  

Sequencing of cancer genomes revealed a rich landscape of somatic single nucleotide variants, structural changes of chromosomes, as well as chromosomal copy number alterations. These chromosome changes are highly variable, and simple translocations, deletions or duplications have been identified, as well as complex events that likely arise through activity of several interconnected processes. Comparison of the cancer genome sequencing data with our knowledge about processes important for maintenance of genome stability, namely DNA replication, repair and chromosome segregation, provides insights into the mechanisms that may give rise to complex chromosomal patterns, such as chromothripsis, a complex form of multiple focal chromosome rearrangements. In addition, observations gained from model systems that recapitulate the rearrangements patterns under defined experimental conditions suggest that mitotic errors and defective DNA replication and repair contribute to their formation. Here, we review the molecular mechanisms that contribute to formation of chromosomal aberrations observed in cancer genomes.



中文翻译:


塑造癌症基因组的过程——从有丝分裂缺陷到染色体重排



癌症基因组测序揭示了丰富的体细胞单核苷酸变异、染色体结构变化以及染色体拷贝数改变。这些染色体变化是高度可变的,并且已经鉴定出简单的易位、缺失或重复,以及可能通过几个相互关联的过程的活动而产生的复杂事件。将癌症基因组测序数据与我们对维持基因组稳定性的重要过程(即 DNA 复制、修复和染色体分离)的知识进行比较,可以深入了解可能产生复杂染色体模式的机制,例如染色体碎裂(一种复杂形式的染色体碎裂)。多焦点染色体重排。此外,从在确定的实验条件下重排重排模式的模型系统中获得的观察结果表明,有丝分裂错误和有缺陷的 DNA 复制和修复有助于其形成。在这里,我们回顾了导致癌症基因组中观察到的染色体畸变形成的分子机制。

更新日期:2021-08-21
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