Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.
DNA Methylation; DNA-Binding Proteins; Ethnic Groups; F-Box-WD Repeat-Containing Protein 7; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genetics, Population; Genome, Human; Genomics; High-Throughput Nucleotide Sequencing; Humans; MicroRNAs; Mutation; Neoplasm Proteins; Neoplasms; Transcription Factors; Von Hippel-Lindau Tumor Suppressor Protein; genomics
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.
Institute for Systems Biology
Carrot-Zhang, Jian; Chambwe, Nyasha; Damrauer, Jeffrey S; Knijnenburg, Theo A; Robertson, A Gordon; Yau, Christina; Zhou, Wanding; Berger, Ashton C; Huang, Kuan-Lin; Newberg, Justin Y; Mashl, R Jay; Romanel, Alessandro; Sayaman, Rosalyn W; Demichelis, Francesca; Felau, Ina; Frampton, Garrett M; Han, Seunghun; Hoadley, Katherine A; Kemal, Anab; Laird, Peter W; Lazar, Alexander J; Le, Xiuning; Oak, Ninad; Shen, Hui; Wong, Christopher K; Zenklusen, Jean C; Ziv, Elad; Cancer Genome Atlas Analysis Network; Cherniack, Andrew D; and Beroukhim, Rameen, "Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer." (2020). Articles, Abstracts, and Reports. 4004.