Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.
Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.
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DOI：
10.1016/j.cell.2011.07.042
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发表时间：
2011-09-16
期刊：
影响因子：
64.5
通讯作者：
Bi W
中科院分区：
文献类型：
--
作者：
Liu P;Erez A;Nagamani SC;Dhar SU;Kołodziejska KE;Dharmadhikari AV;Cooper ML;Wiszniewska J;Zhang F;Withers MA;Bacino CA;Campos-Acevedo LD;Delgado MR;Freedenberg D;Garnica A;Grebe TA;Hernández-Almaguer D;Immken L;Lalani SR;McLean SD;Northrup H;Scaglia F;Strathearn L;Trapane P;Kang SH;Patel A;Cheung SW;Hastings PJ;Stankiewicz P;Lupski JR;Bi W
在基因组疾病中已经观察到由两个或更多个断点连接组成的复杂基因组重排（CGR）。最近，在多种癌症中描述了一种称为chromothripsis的染色体灾难现象，其中许多基因组重排显然是在一个单一的灾难性事件中获得的。在这里，我们表明，宪法获得CGRs共享与癌症chromothripsis的相似性。在研究的17例CGR病例中，我们观察到了定位和多拷贝数变化，包括缺失、重复和/或三重，以及广泛的易位和倒位。基因组重排涉及的大小和复杂性各不相同;在一个案例中，阵列比较基因组杂交显示了18个拷贝数变化。断裂点测序鉴定了特征性特征，包括断裂点处的小模板插入和断裂点连接处的微同源性，这归因于复制过程。CGR和chromothripsis之间的相似性表明了相似的机制基础。这种染色体灾难性事件似乎反映了在生物体的整个生命周期中起作用的基本DNA代谢。
Complex genomic rearrangements (CGR) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated we observed localization and multiple copy number changes including deletions, duplications and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism’s life cycle.
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影响因子：
3.7
作者：
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3.5
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Cuppen, Edwin
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56.9
作者：
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通讯作者：
Eichler, EE
影响因子：
8.8
作者：
Cheung, SW;Shaw, CA;Beaudet, AL
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Beaudet, AL