癌症结构变异和3D基因组学

SCI

27 July 2022

Structural variations in cancer and the 3D genome（Nature Reviews Cancer, IF: 69.8）

Dubois F, Sidiropoulos N, Weischenfeldt J, Beroukhim R. Structural variations in cancer and the 3D genome. Nature Reviews Cancer 2022. DOI: 10.1038/s41568-022-00488-9.

Corresponding author: Joachim Weischenfeldt. joachim.weischenfeldt@bric.ku.dk，Rameen Beroukhim. Rameen Beroukhim@dfci.harvard.edu

Abstract | 摘要

Structural variations (SVs) affect more of the cancer genome than any other type of somatic genetic alteration but difficulties in detecting and interpreting them have limited our understanding. Clinical cancer sequencing also increasingly aims to detect SVs, leading to a widespread necessity to interpret their biological and clinical relevance. Recently, analyses of large whole-genome sequencing data sets revealed features that impact rates of SVs across the genome in different cancers. A striking feature has been the extent to which, in both their generation and their influence on the selective fitness of cancer cells, SVs are more specific to individual cancer types than other genetic alterations such as single-nucleotide variants. This Perspective discusses how the folding of the 3D genome, and differences in its folding across cell types, affect observed SV rates in different cancer types as well as how SVs can impact cancer cell fitness.

相较于其他任何类型的体细胞基因改变，结构变异（SVs）对癌症基因组的影响更多，但是在发现和干预方面的困难限制了我们的理解。临床癌症测序也在越来越多地以发现SVs为目标，导致了阐明它们生物学和临床关联的广泛必要。最近，对大型全基因组测序数据集的分析揭示了影响不同癌症中基因组SVs发生率的特征。SVs的一个显著特征是，在其产生和对癌细胞的选择适应性的影响方面，SVs比其他基因改变（如单核苷酸变异）对单个癌症类型的特异性更强。本文讨论了3D基因组的折叠，以及不同细胞类型的折叠差异，如何影响不同癌症类型中观察到的SVs发生率，以及SVs如何影响癌细胞的适应性。