Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex ménage à trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis.

中文翻译：

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癌症中的非整倍性和染色体不稳定性：混乱的困境。

基因组不稳定性（GIN）是癌细胞的标志，可促进在癌症进化过程中获得赋予侵略性或耐药性表型的突变。染色体不稳定性（CIN）是GIN的一种形式，涉及频繁的细胞遗传学变化，导致染色体拷贝数发生变化（非整倍性）。尽管CIN和非整倍性都是癌细胞的共同特征，但它们在肿瘤发生和发展中的作用尚不清楚。一方面，已知CIN和非整倍性会提供遗传变异，以使细胞适应不断变化的环境，例如营养成分波动和缺氧。具有本构非整倍性的患者更容易患某些类型的癌症，这表明染色体拷贝数的变化可能对癌症的发展有积极作用。另一方面，已经观察到染色体失衡对细胞适应性具有有害作用，并可能触发细胞周期停滞或凋亡。此外，用于CIN的鼠标模型导致了相互矛盾的结果。综上所述，这些发现表明CIN，非整倍性与癌症之间的关系比以前预期的更为复杂。在这里，我们回顾一下关于这种复杂的基因结构的知识，讨论最近的证据表明非整倍性，CIN和GIN共同促进了基因组混乱的恶性循环。最后，我们提出了一个可行的假设，以调和有关非整倍性和CIN在肿瘤发生中作用的矛盾观察。综上所述，这些发现表明CIN，非整倍性与癌症之间的关系比以前预期的更为复杂。在这里，我们回顾一下有关这种复杂的基因结构的知识，讨论最近的证据表明非整倍性，CIN和GIN共同促进了基因组混乱的恶性循环。最后，我们提出了一个可行的假设，以调和有关非整倍性和CIN在肿瘤发生中作用的矛盾观察。综上所述，这些发现表明CIN，非整倍性与癌症之间的关系比以前预期的更为复杂。在这里，我们回顾一下有关这种复杂的基因结构的知识，讨论最近的证据表明非整倍性，CIN和GIN共同促进了基因组混乱的恶性循环。最后，我们提出了一个可行的假设，以调和有关非整倍性和CIN在肿瘤发生中作用的矛盾观察。