刊登在近日国际杂志Nature Communications上的一项基因组分析显示,用于研究工作的一些最流行的卵巢癌细胞系可能并不是卵巢癌的好模型。
从临床肿瘤样本获得的癌细胞系经常用在癌症研究中,并使我们对癌症生物学有了很多新认识。Nikolaus Schultz和他的研究团队分析了来自两个大型基因测序项目的可以公开获得的数据集,这两个项目分别是:“癌症基因组图谱”——确定临床卵巢癌样本的基因组特征;“癌细胞系百科全书”——包含用于研究工作的大约1000个癌细胞系的相似数据。
Schultz的团队对这些数据彼此之间进行了匹配,并根据大约50个卵巢癌细胞系与来自“高等级浆液性卵巢癌” (HGSOC) 患者的临床样本的基因组相似性对它们进行了排序。他们发现,两个最流行的卵巢癌细胞系(占所有已发表的关于HGSOC的研究论文的60%)并不是非常像HGSOC,而12个最适合的卵巢癌细胞系仅用在1%的已发表研究论文中。
该研究提供了一个方法论框架,这个框架也许还可应用于其他细胞系和不同类型的癌症,以便评估它们作为研究工具是否合适。
doi:10.1038/ncomms3126
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Evaluating cell lines as tumour models by comparison of genomic profiles
Silvia Domcke, Rileen Sinha, Douglas A. Levine, Chris Sander & Nikolaus Schultz
Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.