Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
BMC Cancer. 2010 Jan 14;10:15. doi: 10.1186/1471-2407-10-15.
Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.
Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.
The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 +/- 29.9% for the cell lines and 15.9 +/- 18.6% for the tissue specimens.
Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.
细胞系在世界范围内的各种生物医学研究中被广泛应用。然而，目前尚不清楚原发性肿瘤组织中存在的基因组改变是否存在于细胞系中，以及细胞系是否携带细胞系特异性的基因组改变。本研究旨在回答这些问题。
采用基于阵列的比较基因组杂交（CGH）技术，使用 4030 个覆盖基因组分辨率为 1.0 兆碱基的细菌人工染色体（BAC），分析 35 例原发性乳腺癌和 24 例乳腺癌细胞系中的 DNA 拷贝数异常（DCNAs）。比较这两组之间的 DCNAs。应用组织微切割技术对原发性肿瘤组织进行处理，以减少正常组织成分对样本的污染。
细胞系和原发性肿瘤组织中具有 DCNAs 的 BAC 克隆的平均数量分别为 1832（已检出克隆的 45.3%）和 971（24.9%）。在>50%的原发性癌症组织中检测到 1q 和 8q 的增益以及 8p、11q、16q 和 17p 的缺失。这些异常也经常在细胞系中检测到。除了这些改变之外，细胞系还显示出反复出现的基因组改变，包括 5p14-15、20q11 和 20q13 的增益以及 4p13-p16、18q12、18q21、Xq21.1 和 Xq26-q28 的缺失，这些改变在肿瘤组织标本中几乎检测不到。这些被认为是细胞系特异性的 DCNAs。HER2 扩增在细胞系和肿瘤组织中均较为常见，但在细胞系和原发性肿瘤之间存在统计学差异（P = 0.012）；细胞系为 41.3 +/- 29.9%，组织标本为 15.9 +/- 18.6%。
已建立的细胞系携带细胞系特异性的 DCNAs 以及在原发性肿瘤组织中检测到的反复出现的异常。因此，必须强调的是，细胞系并不总是代表其亲本肿瘤组织的基因型。
