美国哈佛大学路德维希中心Peter J. Park团队利用全基因组测序对2658种人类癌症中的着色杆菌病进行了综合分析。该项研究成果2020年2月5日在线发表在《自然—遗传学》上。

作为国际癌症基因组联合会（ICGC）和癌症基因组图谱（TCGA）的泛癌症全基因组分析（PCAWG）联合会的一部分，研究人员使用全基因组测序数据分析了38种癌症类型中2,658个肿瘤样本的着色杆菌病模式。研究发现，在所有癌症中都普遍存在着色杆菌病的发生，在几种癌症类型中，其发生率超过了50％。尽管典型的着色杆菌病具有两个拷贝数状态的振荡，然而相当一部分案例涉及多个染色体和其它结构改变。除了非同源末端连接，研究人员还检测到复制相关过程和模板化插入的特点。着色杆菌病有助于癌基因扩增以及如错配修复相关基因的失活。这些发现表明，在人类癌症中着色杆菌病是驱动基因组进化的主要进程。

据介绍，着色杆菌病是一种突变现象，其特征是发生在癌症和其他疾病中的大规模簇状基因组重排。近年来，在某些癌症类型的研究表明，与最初通过低分辨率拷贝数推断的数据相比，着色杆菌病可能更为普遍。

附：英文原文

Title: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Author: Isidro Corts-Ciriano, Jake June-Koo Lee, Ruibin Xi, Dhawal Jain, Youngsook L. Jung, Lixing Yang, Dmitry Gordenin, Leszek J. Klimczak, Cheng-Zhong Zhang, David S. Pellman, Peter J. Park

Issue&Volume: 2020-02-05

Abstract: 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 2,658tumors from 38cancer 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.

DOI: 10.1038/s41588-019-0576-7

Source: https://www.nature.com/articles/s41588-019-0576-7