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人癌细胞基因组重排导致基因表达失调
作者:小柯机器人 发布时间:2020/2/11 10:44:23

美国德克萨斯大学MD安德森癌症中心P. Andrew Futreal研究组发现人癌细胞中基因组重排破坏染色质折叠结构域。相关论文202025日发表在《自然遗传学》上。

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)联盟汇总了来自38种肿瘤类型的2658例癌症患者的全基因组测序数据,作为该联盟的一部分,他们分析了288,457个躯体结构变异(SV),以了解SV在整个拓扑关联域(TAD)中的分布和影响。值得注意的是,SV可以导致离散TAD融合,复杂的重排显著改变癌症基因组中的染色质折叠图谱。值得注意的是,只有14%的边界缺失导致附近基因表达的变化超过两倍。

据悉,通过组织线性DNA染色质可折叠成连续的层。相同的TAD中的基因表现出相似的表达和组蛋白修饰图谱,并且分隔不同结构域的边界在增强这些功能的稳定性方面具有重要作用。实际上,人类癌症中的结构域破坏会导致基因表达的失调。然而,人类癌症中结构域破坏的频率仍不清楚。

附:英文原文

Title: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

Author: Kadir C. Akdemir, Victoria T. Le, Sahaana Chandran, Yilong Li, Roel G. Verhaak, Rameen Beroukhim, Peter J. Campbell, Lynda Chin, Jesse R. Dixon, P. Andrew Futreal

Issue&Volume: 2020-02-05

Abstract: Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. 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), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.

DOI: 10.1038/s41588-019-0564-y

Source: https://www.nature.com/articles/s41588-019-0564-y

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex