Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

中文翻译：

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使用全基因组测序对 2,658 种人类癌症的染色体碎裂进行综合分析。

染色体碎裂是一种突变现象，其特征是发生在癌症和其他疾病中的大规模、成簇的基因组重排。最近对选定癌症类型的研究表明，染色体碎裂可能比最初从低分辨率拷贝数数据推断的更常见。在这里，作为国际癌症基因组联盟 (ICGC) 和癌症基因组图谱 (TCGA) 的全基因组泛癌症分析 (PCAWG) 联盟的一部分，我们使用全基因组分析了 38 种癌症类型的 2,658 种肿瘤的染色体碎裂模式。基因组测序数据。我们发现，chromothripsis 事件在癌症中普遍存在，在几种癌症类型中发生的频率超过 50%。而典型的染色体碎裂图显示两个拷贝数状态之间的振荡，相当一部分事件涉及多条染色体和额外的结构改变。除了非同源末端连接外，我们还检测复制相关过程和模板化插入的特征。染色体碎裂有助于癌基因扩增和基因失活，例如错配修复相关基因。这些发现表明，染色体碎裂是驱动人类癌症基因组进化的主要过程。