Genome signatures of colon carcinoma cell lines
Genome signatures of colon carcinoma cell lines
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DOI：
10.1016/j.cancergencyto.2004.03.014
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Lothe, RA
中科院分区：
文献类型：
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作者：
Kleivi, K;Teixeira, MR;Lothe, RA
在癌症生物学中，细胞系经常被用来代替原发性肿瘤，因为它们的广泛可用性和体内状态的密切反映。癌症是一种遗传性疾病，通常由小规模和大规模DNA重排引起。因此，了解肿瘤细胞系的基因组谱以使其能够正确和有效地用作实验工具是至关重要的。在这里，我们提出了一个全面的研究20结肠癌细胞系的基因组图谱结合常规核型分析（G显带），比较基因组杂交（CGH），荧光原位杂交（M-FISH）。显示了微卫星不稳定性（MSI）和染色体不稳定性（CIN）细胞系之间的主要差异; CIN细胞系表现出涉及许多染色体的复杂核型（平均值：8.5拷贝数变化），而MSI细胞系表现出相当少的畸变（平均值：2.6）。这3种技术相互补充，以提供表征癌细胞的染色体数量和结构变化的详细图片。因此，7个细胞系（Colo 320、EB、Fri、IS 2、IS 3、SW 480和V9 P）在此首次被完全核型分析，并且其中5个细胞系先前未被细胞遗传学描述。通过层次聚类分析，我们表明，该细胞系是在基因组水平上的原发性癌的代表性模型。我们还提出了肿瘤进展的实验模型的基因组谱，包括从原发性癌建立的3个细胞系（IS 1、IS 2和IS 3），其相应的肝转移和腹膜转移来自同一患者。为了解决克隆性的问题，我们比较了在2个实验室中生长的3种常见细胞系的基因组。最后，我们将所有结果与先前发表的CGH数据和结直肠细胞系的核型进行了比较。总之，细胞系遗传复杂性的巨大变化突出了使用这些研究工具进行功能研究的研究人员全面参考基因组图谱的重要性。(C)2004年爱思唯尔公司All rights reserved.
In cancer biology, cell lines are often used instead of primary tumors because of their widespread availability and close reflection of the in vivo state. Cancer is a genetic disease, commonly caused by small- and large-scale DNA rearrangements. Therefore, it is essential to know the genomic profiles of tumor cell lines to enable their correct and efficient use as experimental tools. Here, we present a comprehensive study of the genomic profiles of 20 colon cancer cell lines combining conventional karyotyping (G-banding), comparative genomic hybridization (CGH), and multicolor fluorescence in situ hybridization (M-FISH). Major differences between the microsatellite instability (MSI) and chromosome instability (CIN) cell lines are shown; the CIN cell lines exhibited complex karyotypes involving many chromosomes (mean: 8.5 copy number changes), whereas the MSI cell lines showed considerably fewer aberrations (mean: 2.6). The 3 techniques complement each other to provide a detailed picture of the numerical and structural chromosomal changes that characterize cancer cells. Therefore, 7 of the cell lines (Colo320, EB, Fri, IS2, IS3, SW480, and V9P) are here completely karyotyped for the first time and, among these, 5 have not previously been cytogenetically described. By hierarchical cluster analysis, we show that the cell lines are representative models for primary carcinomas at the genome level. We also present the genomic profiles of an experimental model for tumor progression, including 3 cell lines (IS 1, IS2, and IS3) established from a primary carcinoma, its corresponding liver- and peritoneal metastasis from the same patient. To address the question of clonality, we compared the genome of 3 common cell lines grown in 2 laboratories. Finally, we compared all our results with previously published CGH data and karyotypes of colorectal cell lines. In conclusion, the large variation in genetic complexity of the cell lines highlights the importance of a comprehensive reference of genomic profiles for investigators engaged in functional studies using these research tools. (C) 2004 Elsevier Inc. All rights reserved.