Department of Computational Biology, Memorial Sloan-Kettering Cancer Center, 417 E 68th St, New York, New York 10065, USA.
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1498, New York, New York 10029, USA.
Nat Commun. 2017 May 10;8:15165. doi: 10.1038/ncomms15165.
The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.
癌细胞系的实用性受到与内源性肿瘤细胞相似性的影响。在这里，我们将癌症细胞系百科全书和 COSMIC 细胞系项目中的 65 个来自肾脏的细胞系的基因组数据与癌症基因组图谱中的三种肾细胞癌亚型进行比较：透明细胞肾细胞癌（ccRCC，也称为肾透明细胞癌）、乳头状（pRCC，也称为肾乳头状）和嫌色细胞癌（chRCC，也称为肾嫌色细胞癌）。聚类拷贝数改变表明，大多数细胞系类似于 ccRCC，少数（包括一些常被用作 ccRCC 模型的细胞系）类似于 pRCC，没有细胞系类似于 chRCC。与细胞系聚类的人类 ccRCC 肿瘤显示出更具侵袭性疾病的临床和基因组特征，这表明细胞系最能代表侵袭性肿瘤。我们根据数据库之间的一致性对重要的肾癌基因的突变和拷贝数改变进行分层，并根据已建立的基于基因表达的惰性和侵袭性亚型对细胞系进行分类。我们的结果可以帮助研究人员分析合适的肾癌细胞系。
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