Oncins Anna, Velten Jessica, Beekman Renée
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Med Res Arch. 2024 Dec 29;12(12). doi: 10.18103/mra.v12i12.6212. eCollection 2025 Jan 1.
Translocations are rearrangements produced upon erroneous repair of double-strand breaks, fusing segments of non-homologous chromosomes. These events can cause chimeric protein expression and other transcriptional alterations, eventually driving oncogenic transformation. Despite their significance, the factors shaping the heterogeneous translocation landscape in healthy individuals and cancer patients remain incompletely understood. In this review, we focus on genomic content and activation as two fundamental factors associated with translocation formation and selection. While emphasizing the critical role of double-strand breaks and interchromosomal contacts in translocation formation, we discuss that selective advantage is likely the main driver shaping translocation landscapes in health and disease. Finally, we address that it remains difficult to disentangle the effect of translocation formation from the influence of selective pressure, and point out that unraveling their separate contribution in future studies will be key to better understand early tumorigenesis.
易位是双链断裂错误修复后产生的重排，会使非同源染色体片段融合。这些事件可导致嵌合蛋白表达及其他转录改变，最终驱动致癌转化。尽管其意义重大，但塑造健康个体和癌症患者中异质易位格局的因素仍未完全明确。在本综述中，我们聚焦于基因组内容和激活这两个与易位形成及选择相关的基本因素。在强调双链断裂和染色体间接触在易位形成中的关键作用的同时，我们讨论了选择优势可能是塑造健康和疾病中易位格局的主要驱动力。最后，我们指出，区分易位形成的影响和选择压力的影响仍然困难，并指出在未来研究中阐明它们各自的作用对于更好地理解早期肿瘤发生至关重要。
