Royal Netherlands Academy of Arts and Sciences (KNAW), Hubrecht Institute, Uppsalalaan 8, 3584CT, Utrecht, the Netherlands.
University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, the Netherlands.
Chromosome Res. 2023 Oct 21;31(4):31. doi: 10.1007/s10577-023-09741-9.
Aneuploidy-the karyotype state in which the number of chromosomes deviates from a multiple of the haploid chromosome set-is common in cancer, where it is thought to facilitate tumor initiation and progression. However, it is poorly tolerated in healthy cells: during development and tissue homeostasis, aneuploid cells are efficiently cleared from the population. It is still largely unknown how cancer cells become, and adapt to being, aneuploid. P53, the gatekeeper of the genome, has been proposed to guard against aneuploidy. Aneuploidy in cancer genomes strongly correlates with mutations in TP53, and p53 is thought to prevent the propagation of aneuploid cells. Whether p53 also participates in preventing the mistakes in cell division that lead to aneuploidy is still under debate. In this review, we summarize the current understanding of the role of p53 in protecting cells from aneuploidy, and we explore the consequences of functional p53 loss for the propagation of aneuploidy in cancer.
非整倍体——染色体数目偏离单倍体染色体组倍数的核型状态——在癌症中很常见，人们认为它有助于肿瘤的发生和发展。然而，它在健康细胞中很难被容忍：在发育和组织稳态过程中，非整倍体细胞会从群体中被有效清除。目前仍不清楚癌细胞是如何成为非整倍体的，以及如何适应非整倍体状态。基因组的守护者 p53 被认为可以防止非整倍体。癌症基因组中的非整倍体与 TP53 基因突变强烈相关，人们认为 p53 可以阻止非整倍体细胞的增殖。p53 是否也参与防止导致非整倍体的细胞分裂错误仍存在争议。在这篇综述中，我们总结了目前对 p53 保护细胞免受非整倍体的作用的理解，并探讨了功能性 p53 缺失对癌症中非整倍体增殖的影响。
