TY - JOUR
T1 - Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer
AU - Cancer Genome Atlas Analysis Network
AU - Carrot-Zhang, Jian
AU - Chambwe, Nyasha
AU - Damrauer, Jeffrey S.
AU - Knijnenburg, Theo A.
AU - Robertson, A. Gordon
AU - Yau, Christina
AU - Zhou, Wanding
AU - Berger, Ashton C.
AU - Huang, Kuan lin
AU - Newberg, Justin Y.
AU - Mashl, R. Jay
AU - Romanel, Alessandro
AU - Sayaman, Rosalyn W.
AU - Demichelis, Francesca
AU - Felau, Ina
AU - Frampton, Garrett M.
AU - Han, Seunghun
AU - Hoadley, Katherine A.
AU - Kemal, Anab
AU - Laird, Peter W.
AU - Lazar, Alexander J.
AU - Le, Xiuning
AU - Oak, Ninad
AU - Shen, Hui
AU - Wong, Christopher K.
AU - Zenklusen, Jean C.
AU - Ziv, Elad
AU - Aguet, Francois
AU - Ding, Li
AU - Demchok, John A.
AU - Mensah, Michael K.A.
AU - Caesar-Johnson, Samantha
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Alfoldi, Jessica
AU - Karczewski, Konrad J.
AU - MacArthur, Daniel G.
AU - Meyerson, Matthew
AU - Benz, Christopher
AU - Stuart, Joshua M.
AU - Cherniack, Andrew D.
AU - Beroukhim, Rameen
N1 - Funding Information:
We thank the National Cancer Institute, United States for funding through U24 grants CA210999, CA210974, CA211006, CA210949, CA210978, CA210952, CA210989, CA210957, CA210990, CA211000, CA210950, CA210969, CA210988, and K24CA169004 and R01CA1845851. J.C.-Z. holds a Banting fellowship. We are grateful for advice from numerous colleagues, TCGA and GDAN collaborators, and the GDC technical support team. J.C.-Z. K.H. S.H. R.J.M. J.Y.N. A.R. R.W.S. F.D. and E.Z. generated ancestry calls. J.C.-Z. N.C. A.C.B. J.S.D. K.H. T.A.K. A.G.R. C.Y. W.Z. and J.Y.N. analyzed the data. A.K. I.F. J.C.-Z. and The Cancer Genome Atlas Research Network provided project administration. A.D.C. and R.B. provided supervision. J.C.-Z. N.C. J.S.D. T.A.K. A.G.R. C.Y. W.Z. A.C.B. K.H. X.L. K.A.H. P.W.L. A.D.C. and R.B. wrote and all authors reviewed the manuscript. J.Y.N. and G.M.F. are employees of Foundation Medicine and shareholders of Roche. X.L. receives a consultant/advisory fee from Eli Lilly, AstraZeneca, and EMD Serono and research funds from Eli Lilly, Boehringer Ingelheim. P.W.L. is on the Scientific Advisory Boards of AnchorDx and Progenity. A.D.C. receives research funding from Bayer. R.B. owns equity in Ampressa Therapeutics and receives research funding from Novartis.
Funding Information:
J.Y.N. and G.M.F. are employees of Foundation Medicine and shareholders of Roche. X.L. receives a consultant/advisory fee from Eli Lilly, AstraZeneca, and EMD Serono and research funds from Eli Lilly, Boehringer Ingelheim. P.W.L. is on the Scientific Advisory Boards of AnchorDx and Progenity. A.D.C. receives research funding from Bayer. R.B. owns equity in Ampressa Therapeutics and receives research funding from Novartis.
Funding Information:
We thank the National Cancer Institute, United States for funding through U24 grants CA210999 , CA210974 , CA211006 , CA210949 , CA210978 , CA210952 , CA210989 , CA210957 , CA210990 , CA211000 , CA210950 , CA210969 , CA210988 , and K24CA169004 and R01CA1845851 . J.C.-Z. holds a Banting fellowship. We are grateful for advice from numerous colleagues, TCGA and GDAN collaborators, and the GDC technical support team.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/5/11
Y1 - 2020/5/11
N2 - 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.
AB - 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.
KW - TCGA
KW - admixture
KW - ancestry
KW - cancer
KW - eQTL
KW - genomics
KW - mRNA
KW - methylation
KW - miRNA
KW - mutation
UR - http://www.scopus.com/inward/record.url?scp=85084180652&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2020.04.012
DO - 10.1016/j.ccell.2020.04.012
M3 - Article
C2 - 32396860
AN - SCOPUS:85084180652
SN - 1535-6108
VL - 37
SP - 639-654.e6
JO - Cancer Cell
JF - Cancer Cell
IS - 5
ER -