小柯机器人

英国剑桥大学Peter J. Campbell、美国博德研究所Rameen Beroukhim和丹麦哥本哈根大学Joachim Weischenfeldt合作揭示人类癌症基因组中体细胞结构变异模式。相关论文2020年2月5日在线发表在《自然》杂志上。

他们使用国际癌症基因组协会（ICGC）和癌症基因组图谱（TCGA）的全基因组全癌基因分析（PCAWG）协会的数据，开发了对来自38种肿瘤的2658例癌症的全基因组测序数据的体细胞结构变异进行分组、分类和描述的方法。出现了十六种结构变异的特征。缺失具有多峰大小分布，在各种肿瘤类型和患者中分布不均，在晚期复制区域富集并与倒位相关。串联复制也具有多峰大小分布，但是在早期复制区域中富集即不平衡易位。基于复制的重排机制可生成具有低拷贝数和频繁倒位重排的各种染色体结构。一种突出的结构由从基因组不同区域复制的2-7个模板组成，这些模板在一个基因座内串在一起。这种模板插入的循环与串联重复相关，并且在肝癌中频繁激活端粒酶基因TERT。癌症中存在各种各样的重排过程，这些重排过程会产生复杂的基因组构型，从而可以进行选择。

研究人员表示，癌症中一个关键的突变过程是结构变异，其中重排删除、扩增或重新排列过程发生在某些碱基到整个染色体的基因组片段上。

附：英文原文

Title: Patterns of somatic structural variation in human cancer genomes

Author: Yilong Li, Nicola D. Roberts, Jeremiah A. Wala, Ofer Shapira, Steven E. Schumacher, Kiran Kumar, Ekta Khurana, Sebastian Waszak, Jan O. Korbel, James E. Haber, Marcin Imielinski, Joachim Weischenfeldt, Rameen Beroukhim, Peter J. Campbell

Issue&Volume: 2020-02-05

Abstract: A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1,2,3,4,5,6,7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.

DOI: 10.1038/s41586-019-1913-9

Source: https://www.nature.com/articles/s41586-019-1913-9

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