Stable karyotypes in epithelial cancer cell lines despite high rates of ongoing structural and numerical chromosomal instability

Stable karyotypes in epithelial cancer cell lines despite high rates of ongoing structural and numerical chromosomal instability
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DOI:
10.1038/sj.neo.7900197
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发表时间:
2002-01-01
期刊:
影响因子:
4.8
通讯作者:
Kirsch, IR
Kirsch, IR
中科院分区:
医学2区
文献类型:
--
作者:
Roschke, AV;Stover, K;Kirsch, IR

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大多数人类肿瘤和肿瘤细胞系表现出数量和结构上的染色体异常。这项研究的目的是确定在选定的癌细胞系中结构和数量不稳定的持续比率,并调查这些比率对核型进展的影响。我们研究了两个结直肠癌细胞系(HCT-116和HT-29)和两个卵巢癌细胞系(SKOV-3和OVCAR-8)及其单细胞亚系。我们发现,所有四个细胞系的标志性核型都是不同的,每个都是异常的。虽然在所有细胞系中都可以证明持续的结构和/或数字染色体不稳定性很高,但在许多世代中共识的核型是相对稳定的。没有出现新的克隆结构染色体重组,核型的少量数量变化仅限于异常染色体。这意味着在细胞培养条件下的一种基因组优化,并暗示了基因组稳定和细胞繁殖之间的联系。我们已经能够通过计算机建模来支持这种可能性。我们没有观察到具有复制错误表型(RER+)的细胞系与其他细胞系在数量或结构不稳定性方面的显著差异。
Most human tumors and tumor cell lines exhibit numerical and structural chromosomal abnormalities. The goal of this study was to determine the ongoing rates of structural and numerical instability in selected cancer cell lines and to investigate the consequences of these rates to karyotypic progression. We studied two colorectal (HCT-116 and HT-29) and two ovarian (SKOV-3 and OVCAR-8) cancer cell lines and their single cell subclones. We found that the signature karyotypes of all four cell lines were distinct and each aberrant. Whereas high rates of ongoing structural and/or numerical chromosomal instability could be demonstrated in all cell lines, there was a relative stability of the consensus karyotype over many generations. No new clonal structural chromosomal reconfigurations emerged and the few numerical changes of karyotypes were restricted to abnormal chromosomes. This implies a kind of genomic optimization under the conditions of cell culture and suggests a link between genomic stabilization and cell propagation. We have been able to support this possibility by computer modeling. We did not observe a profound difference in the rates of numerical or structural instability in the cell lines with a replication error phenotype (RER+) versus the other cell lines.