van den Brand Teun, Collier Maria Donaldson, Flach Koen D, Gregoricchio Sebastian, Mayayo-Peralta Isabel, Dauyey Zhanna, Schuurman Karianne, Teunissen Hans, Zwart Wilbert, de Wit Elzo
Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Division of Oncogenomics, Oncode Institute & Netherlands Cancer Institute, Amsterdam, the Netherlands.
iScience. 2025 Aug 5;28(9):113268. doi: 10.1016/j.isci.2025.113268. eCollection 2025 Sep 19.
During cancer development and progression massive alterations in gene expression are observed. Gene regulation occurs within the context of the 3D genome. However, the impact of disease progression on 3D genome organization remains poorly understood. Using breast cancer as a model, we have profiled the 3D genome throughout the natural course of the disease; from development to progression. Uniquely, we analyzed tumors from the same patients, enabling us to gauge the extent of changes that happen upon metastasis. Our results show that the organization of the genome at the level of topologically associating domains (TADs) and compartments upon tumorigenesis and metastasis, is remarkably stable. However, in pleural metastases, representing heavily pretreated progressive disease, the 3D genome is massively affected, and highly heterogeneous between patients, both on the compartment and TAD level. Our data reveal that disease progression in breast cancer is associated with a progressive unraveling of the 3D genome.
在癌症发生和发展过程中，会观察到基因表达的大量改变。基因调控发生在三维基因组的背景下。然而，疾病进展对三维基因组组织的影响仍知之甚少。以乳腺癌为模型，我们在疾病的自然进程中，从发生到进展，对三维基因组进行了分析。独特的是，我们分析了同一患者的肿瘤，从而能够评估转移时发生的变化程度。我们的结果表明，在肿瘤发生和转移时，拓扑相关结构域（TADs）和区室水平上的基因组组织非常稳定。然而，在代表经过大量预处理的进展性疾病的胸膜转移中，三维基因组受到极大影响，并且在患者之间，无论是在区室还是TAD水平上，都高度异质。我们的数据表明，乳腺癌的疾病进展与三维基因组的逐步解聚有关。
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