Human chromosomes are large spatially and hierarchically structured entities, the integrity of which needs to be preserved throughout the lifespan of the cell and in conjunction with cell cycle progression. Preservation of chromosomal structure is important for proper deployment of cell type-specific gene expression programs. Thus, aberrations in the integrity and structure of chromosomes will predictably lead to disease, including cancer. Here, we provide an updated standpoint with respect to chromatin misfolding and the emergence of various cancer types. We discuss recent studies implicating the disruption of topologically associating domains, switching between active and inactive compartments, rewiring of promoter–enhancer interactions in malignancy as well as the effects of single nucleotide polymorphisms in non-coding regions involved in long-range regulatory interactions. In light of these findings, we argue that chromosome conformation studies may now also be useful for patient diagnosis and drug target discovery.

中文翻译：

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空间基因组结构和恶性肿瘤的出现。

人类染色体是大的空间和层次结构实体，其完整性需要在细胞的整个生命周期中以及与细胞周期进程一起保持。保留染色体结构对于正确部署细胞类型特异性基因表达程序很重要。因此，染色体完整性和结构的异常将可预见地导致疾病，包括癌症。在这里，我们提供了关于染色质错误折叠和各种癌症类型出现的最新观点。我们讨论了最近的研究，这些研究涉及拓扑关联域的破坏，在活动和非活动区室之间切换，恶性肿瘤中启动子-增强子相互作用的重新布线以及单核苷酸多态性在参与长程调控相互作用的非编码区的影响。鉴于这些发现，我们认为染色体构象研究现在也可能对患者诊断和药物靶点发现有用。