Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer
Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer
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DOI：
10.1016/j.ccell.2020.04.012
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发表时间：
2020-05-11
期刊：
影响因子：
50.3
通讯作者：
Beroukhim, Rameen
中科院分区：
文献类型：
--
作者：
Carrot-Zhang, Jian;Chambwe, Nyasha;Beroukhim, Rameen
我们评估了来自癌症基因组图谱的33种癌症类型的10678名患者的祖先对突变率、DNA甲基化、mRNA和miRNA表达的影响。我们证明了癌症亚型和与祖先相关的技术产物是重要的混杂因素，但没有得到充分的解释。一旦得到解释，与祖先相关的差异跨越了所有分子特征和数百个基因。生物学上的显著差异通常是组织特异性的，而不是癌症特异性的。然而，混合和通路分析表明，其中一些差异与癌症有因果关系。具体发现包括非洲裔患者FBXW7突变增加，非洲裔肾癌患者VHL和PBRM1突变减少，东亚裔膀胱癌患者免疫活性降低。
We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Biologically significant differences were usually tissue specific but not specific to cancer. However, admixture and pathway analyses suggested some of these differences are causally related to cancer. Specific findings included increased FBXW7 mutations in patients of African origin, decreased VHL and PBRM1 mutations in renal cancer patients of African origin, and decreased immune activity in bladder cancer patients of East Asian origin.