Centre de Recherche sur le Cancer, CHU de Québec-Université Laval, Québec City, QC, Canada.
Centre de recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Axe de reproduction, santé de la mère et de l'enfant, Québec, QC, Canada.
Oncogene. 2024 Oct;43(43):3139-3150. doi: 10.1038/s41388-024-03163-5. Epub 2024 Sep 15.
Mitotic cells face the challenging task of ensuring accurate and equal segregation of their duplicated, condensed chromosomes between the nascent daughter cells. Errors in the process result in chromosome missegregation, a significant consequence of which is the emergence of aneuploidy-characterized by an imbalance in chromosome number-and the associated phenomenon of chromosome instability (CIN). Aneuploidy and CIN are common features of cancer, which leverages them to promote genome heterogeneity and plasticity, thereby facilitating rapid tumor evolution. Recent research has provided insights into how mitotic errors shape cancer genomes by inducing both numerical and structural chromosomal changes that drive tumor initiation and progression. In this review, we survey recent findings regarding the mitotic causes and consequences of aneuploidy. We discuss new findings into the types of chromosome segregation errors that lead to aneuploidy and novel pathways that protect genome integrity during mitosis. Finally, we describe new developments in our understanding of the immediate consequences of chromosome mis-segregation on the genome stability of daughter cells.
有丝分裂细胞面临着一项艰巨的任务,即确保其复制、浓缩的染色体在新形成的子细胞之间准确且均等的分离。如果这一过程中出现错误,就会导致染色体错误分离,其一个重要后果是出现非整倍体——以染色体数量失衡为特征——以及随之而来的染色体不稳定性(CIN)现象。非整倍体和 CIN 是癌症的常见特征,癌症利用这些特征来促进基因组异质性和可塑性,从而促进肿瘤的快速进化。最近的研究提供了一些见解,即有丝分裂错误如何通过诱导数值和结构染色体变化来塑造癌症基因组,从而推动肿瘤的起始和进展。在这篇综述中,我们调查了关于非整倍体的有丝分裂原因和后果的最新发现。我们讨论了导致非整倍体的染色体分离错误的类型,以及在有丝分裂过程中保护基因组完整性的新途径。最后,我们描述了我们对染色体错误分离对子代细胞基因组稳定性的直接后果的理解的新进展。