Division of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Neurosurgery, Kurume University, School of Medicine, Kurume, Japan.
Cancer Sci. 2022 Nov;113(11):3864-3876. doi: 10.1111/cas.15544. Epub 2022 Sep 9.
Aneuploidy arises from persistent chromosome segregation errors, or chromosomal instability. Although it has long been known as a hallmark of cancer cells, reduced cellular fitness upon induced ploidy alterations hinders the understanding of how aneuploidy relates to cancer development in the body. In this study, we used FISH analysis targeting centromeres to indicate ploidy changes, and quantitatively evaluated the ploidy statuses of gastric tumors derived from a total of 214 patients, ranging from early to advanced disease. We found that cancer cells reveal a marked elevation of aneuploid population, increasingly in cases diagnosed in advanced stages. The expansion of the aneuploid population is well associated with p53 deficiency, consistent with its essential role in genome maintenance. Comparisons among multiple locations within the tumor, or between the primary and metastatic tumors, indicated that cancer cells mostly retain their ploidy alterations throughout primary tumors, but metastatic tumors may consist of cells with either increased or decreased levels of aneuploidy. We also found that a notable proportion of polyploid cells are often already present in chronic gastritis epithelia. These observations underscore that chromosome-level variations are widespread in gastric cancers, shaping their genetic heterogeneity and malignant properties.
非整倍体是由于染色体分离错误或染色体不稳定引起的。尽管它长期以来一直被认为是癌细胞的一个特征，但诱导的倍性改变导致细胞适应性降低，这阻碍了我们理解非整倍体与体内癌症发展的关系。在这项研究中，我们使用针对着丝粒的 FISH 分析来指示倍性变化，并定量评估了总共 214 名患者的胃肿瘤的倍性状态，这些患者的疾病从早期到晚期不等。我们发现，癌细胞中存在明显的非整倍体群体升高，在晚期诊断的病例中更为明显。非整倍体群体的扩张与 p53 缺失密切相关，这与其在基因组维护中的重要作用一致。对肿瘤内多个部位或原发肿瘤与转移肿瘤之间的比较表明，癌细胞在原发肿瘤中大多保留其倍性改变，但转移肿瘤可能包含具有增加或减少非整倍体水平的细胞。我们还发现，在慢性胃炎上皮中经常已经存在相当比例的多倍体细胞。这些观察结果强调了染色体水平的变异在胃癌中广泛存在，塑造了它们的遗传异质性和恶性特征。
