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.
Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer / Carrot-Zhang, Jian; Chambwe, Nyasha; Damrauer, Jeffrey S.; Knijnenburg, Theo A.; Robertson, A. Gordon; Yau, Christina; Zhou, Wanding; Berger, Ashton C.; Huang, Kuan-Iin; 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.; Beroukhim, Rameen. - In: CANCER CELL. - ISSN 1535-6108. - 37:5(2020), pp. 639-654.e6. [10.1016/j.ccell.2020.04.012]
Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer
Romanel, Alessandro;Demichelis, Francesca;
2020-01-01
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.| File | Dimensione | Formato | |
|---|---|---|---|
|
1-s2.0-S1535610820302117-main.pdf
Solo gestori archivio
Tipologia:
Versione editoriale (Publisher’s layout)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
5.12 MB
Formato
Adobe PDF
|
5.12 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione
