Karyotypic complexity of the NCI-60 drug-screening panel.
Karyotypic complexity of the NCI-60 drug-screening panel.
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发表时间：
2003-12
期刊：
影响因子：
11.2
通讯作者：
A. Roschke;G. Tonon;Kristen S Gehlhaus;Nicolas McTyre;K. Bussey;S. Lababidi;D. Scudiero;J. Weinstein;I. Kirsch
中科院分区：
文献类型：
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作者：
A. Roschke;G. Tonon;Kristen S Gehlhaus;Nicolas McTyre;K. Bussey;S. Lababidi;D. Scudiero;J. Weinstein;I. Kirsch
我们使用光谱核型分析提供了一个详细的分析，核型畸变的不同群体的癌细胞系建立的国家癌症研究所的抗癌药物发现的目的。沿着这些细胞系的核型描述，我们基于基因组解剖学的三个独立组成部分定义并研究了核型复杂性和异质性（中期-中期变异）：（a）倍性;（B）数值变化;和（c）结构重排。在这些细胞系中，这些参数的变化很大，并且揭示了它们之间不同的关联模式。对整个细胞系或特定谱系内染色体变化的断点和其他特定特征的分析指出，区分上皮肿瘤细胞系的着丝粒区域具有显著的不稳定性。我们还发现，平衡易位在来自实体瘤和造血肿瘤的细胞系中的绝对数量上一样频繁。在癌细胞系和原发性肿瘤中观察到的核型变化之间存在重要的相似性。该数据集提供了对肿瘤发展和进展期间可能发生的不稳定事件和染色体不稳定性的原因和后果的见解。它还为研究结构基因组解剖学与癌症分子标记和靶点、基因表达、基因剂量以及对数万种分子化合物的抗性或敏感性之间的关联提供了基础。
We used spectral karyotyping to provide a detailed analysis of karyotypic aberrations in the diverse group of cancer cell lines established by the National Cancer Institute for the purpose of anticancer drug discovery. Along with the karyotypic description of these cell lines we defined and studied karyotypic complexity and heterogeneity (metaphase-to-metaphase variations) based on three separate components of genomic anatomy: (a) ploidy; (b) numerical changes; and (c) structural rearrangements. A wide variation in these parameters was evident in these cell lines, and different association patterns between them were revealed. Analysis of the breakpoints and other specific features of chromosomal changes across the entire set of cell lines or within particular lineages pointed to a striking lability of centromeric regions that distinguishes the epithelial tumor cell lines. We have also found that balanced translocations are as frequent in absolute number within the cell lines derived from solid as from hematopoietic tumors. Important similarities were noticed between karyotypic changes in cancer cell lines and that seen in primary tumors. This dataset offers insights into the causes and consequences of the destabilizing events and chromosomal instability that may occur during tumor development and progression. It also provides a foundation for investigating associations between structural genome anatomy and cancer molecular markers and targets, gene expression, gene dosage, and resistance or sensitivity to tens of thousands of molecular compounds.