癌症遗传祖源的综合分析及其分子相关性
Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.
机构信息
The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Institute for Systems Biology, Seattle, WA 98109, USA.
出版信息
Cancer Cell. 2020 May 11;37(5):639-654.e6. doi: 10.1016/j.ccell.2020.04.012.
Abstract
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.
摘要
我们评估了癌症基因组图谱中 33 种癌症类型的 10678 名患者的遗传背景对突变率、DNA 甲基化以及 mRNA 和 miRNA 表达的影响。结果表明，癌症亚型和与遗传相关的技术伪影是重要的混杂因素，但以前的研究并未充分考虑到这些因素。一旦考虑到这些因素，与遗传相关的差异就会跨越所有分子特征和数百个基因。具有生物学意义的差异通常是组织特异性的，而不是癌症特异性的。然而，混合分析和通路分析表明，这些差异中的一些与癌症有因果关系。具体的发现包括：非洲裔患者中 FBXW7 突变增加，非洲裔肾细胞癌患者中 VHL 和 PBRM1 突变减少，以及东亚裔膀胱癌患者的免疫活性降低。
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