Ancestral characterization of 1018 cancer cell lines highlights disparities and reveals gene expression and mutational differences
Ancestral characterization of 1018 cancer cell lines highlights disparities and reveals gene expression and mutational differences
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DOI：
10.1002/cncr.32020
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发表时间：
2019-06-15
期刊：
影响因子：
6.2
通讯作者：
O'Connor, Timothy D.
中科院分区：
文献类型：
--
作者：
Kessler, Michael D.;Bateman, Nicholas W.;O'Connor, Timothy D.
背景虽然细胞系是研究癌症生物学的重要资源，但许多细胞系的祖先起源未知，并且它们的使用可能不是评估所有患者群体生物学的最佳选择。方法 使用来自癌症体细胞突变目录 (COSMIC) 细胞系项目的全基因组芯片数据进行混合分析，以计算 1018 个癌细胞系的遗传祖先估计值。按组织和组织学类型进行分层分析后，使用线性模型评估血统对基因表达和体细胞突变频率的影响。结果 对于701个未报告血统的细胞系，215个来自东亚，30个来自非洲或非裔美国人，453个来自欧洲。在不同组织类型的祖先代表性中观察到显着的不平衡，大多数分析的组织类型几乎没有非裔美国人祖先起源的细胞系，并且所有细胞系中几乎完全不存在西班牙裔和南亚裔祖先。在评估这些细胞系的基因表达时，基因 Neurobeachin line 1 (NBEAL1)、溶质载体家族 6 成员 19 (SLC6A19)、HEAT 重复包含 6 (HEATR6) 和上皮细胞转化 2 样 (ECT2L) 的表达水平与祖先相关。在不同祖先比例的细胞系中，体细胞突变类型的比例也存在显着差异。结论 通过估计 1018 个癌细胞系的遗传祖先，作者提供了一种资源，癌症研究人员可以使用该资源来确保他们的细胞系在祖先上代表了他们想要影响的人群。此外，发现的新的祖先特异性信号强调了研究癌症时祖先意识的重要性。
Background Although cell lines are an essential resource for studying cancer biology, many are of unknown ancestral origin, and their use may not be optimal for evaluating the biology of all patient populations. Methods An admixture analysis was performed using genome-wide chip data from the Catalogue of Somatic Mutations in Cancer (COSMIC) Cell Lines Project to calculate genetic ancestry estimates for 1018 cancer cell lines. After stratifying the analyses by tissue and histology types, linear models were used to evaluate the influence of ancestry on gene expression and somatic mutation frequency. Results For the 701 cell lines with unreported ancestry, 215 were of East Asian origin, 30 were of African or African American origin, and 453 were of European origin. Notable imbalances were observed in ancestral representation across tissue type, with the majority of analyzed tissue types having few cell lines of African American ancestral origin, and with Hispanic and South Asian ancestry being almost entirely absent across all cell lines. In evaluating gene expression across these cell lines, expression levels of the genes neurobeachin line 1 (NBEAL1), solute carrier family 6 member 19 (SLC6A19), HEAT repeat containing 6 (HEATR6), and epithelial cell transforming 2 like (ECT2L) were associated with ancestry. Significant differences were also observed in the proportions of somatic mutation types across cell lines with varying ancestral proportions. Conclusions By estimating genetic ancestry for 1018 cancer cell lines, the authors have produced a resource that cancer researchers can use to ensure that their cell lines are ancestrally representative of the populations they intend to affect. Furthermore, the novel ancestry-specific signal identified underscores the importance of ancestral awareness when studying cancer.