Federico Concetta, Brancato Desiree, Bruno Francesca, Coniglio Elvira, Sturiale Valentina, Saccone Salvatore
Department of Biological, Geological and Environmental Sciences, University of Catania, 95124 Catania, Italy.
Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy.
Genes (Basel). 2025 Jun 30;16(7):780. doi: 10.3390/genes16070780.
The spatial organization of the genome within the nucleus is a fundamental regulator of gene expression, genome stability, and cell identity. This review addresses the central question of how nuclear genome architecture contributes to disease mechanisms and diagnostics, and how technological advances enable its clinical exploration. We first outline the principles of nuclear genome architecture, including chromosome territories, replication timing, and 3D domains, and their role in gene regulation and disease. We then explore the mechanisms and consequences of chromosomal rearrangements, and how replication dynamics intersect with epigenetic regulation and genome stability. Diagnostic tools are presented in chronological progression, from conventional cytogenetics to high-resolution genomic and single-cell techniques. A dedicated section focuses on cancer cytogenomics and its clinical implications. We further highlight emerging technologies for 3D genome and epigenome profiling and their integration into diagnostic workflows. Finally, we discuss current challenges, such as standardization and cost, and the transformative potential of multi-omics and artificial intelligence for future precision diagnostics. Overall, we provide a comprehensive overview of how cytogenetics and cytogenomics contribute to the understanding and clinical diagnosis of genetic and neoplastic diseases.
细胞核内基因组的空间组织是基因表达、基因组稳定性和细胞特性的基本调节因子。本综述探讨了一个核心问题，即核基因组结构如何促成疾病机制和诊断，以及技术进步如何推动其临床探索。我们首先概述核基因组结构的原理，包括染色体领地、复制时间和三维结构域，以及它们在基因调控和疾病中的作用。然后，我们探讨染色体重排的机制和后果，以及复制动态如何与表观遗传调控和基因组稳定性相互作用。诊断工具按照时间顺序依次介绍，从传统细胞遗传学技术到高分辨率基因组技术和单细胞技术。一个专门的部分聚焦于癌症细胞基因组学及其临床意义。我们进一步强调用于三维基因组和表观基因组分析的新兴技术，以及它们如何整合到诊断工作流程中。最后，我们讨论当前面临的挑战，如标准化和成本问题，以及多组学和人工智能在未来精准诊断中的变革潜力。总体而言，我们全面概述了细胞遗传学和细胞基因组学如何有助于理解和临床诊断遗传疾病和肿瘤疾病。
