Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.

DNA Methylation DNA-Binding Proteins / genetics Ethnicity / genetics F-Box-WD Repeat-Containing Protein 7 / genetics Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Genetics, Population Genome, Human Genomics High-Throughput Nucleotide Sequencing Humans MicroRNAs / genetics Mutation Neoplasm Proteins / genetics Neoplasms / ethnology Transcription Factors / genetics Von Hippel-Lindau Tumor Suppressor Protein / genetics
TCGA admixture ancestry cancer eQTL genomics mRNA methylation miRNA mutation

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
11 05 2020
Historique:
received: 04 06 2019
revised: 31 12 2019
accepted: 13 04 2020
entrez: 13 5 2020
pubmed: 13 5 2020
medline: 4 11 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ccell.2020.04.012 PMID: 32396860 PMC: PMC7328015
pubmed: 32396860
pii: S1535-6108(20)30211-7
doi: 10.1016/j.ccell.2020.04.012
pmc: PMC7328015
mid: NIHMS1589126
pii:
doi:

Substances chimiques

DNA-Binding Proteins 0
F-Box-WD Repeat-Containing Protein 7 0
FBXW7 protein, human 0
MicroRNAs 0
Neoplasm Proteins 0
PBRM1 protein, human 0
Transcription Factors 0
Von Hippel-Lindau Tumor Suppressor Protein EC 2.3.2.27
VHL protein, human EC 6.3.2.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

639-654.e6

Subventions

Organisme : NCI NIH HHS
ID : U24 CA210978
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227466
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227237
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA194547
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210974
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210989
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210952
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210957
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210949
Pays : United States
Organisme : NCI NIH HHS
ID : K24 CA169004
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA221709
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA211000
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210950
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA184585
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210969
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210988
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA211006
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210999
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA264027
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210990
Pays : United States

Investigateurs

Francois Aguet (F)
Li Ding (L)
John A Demchok (JA)
Michael K A Mensah (MKA)
Samantha Caesar-Johnson (S)
Roy Tarnuzzer (R)
Zhining Wang (Z)
Liming Yang (L)
Jessica Alfoldi (J)
Konrad J Karczewski (KJ)
Daniel G MacArthur (DG)
Matthew Meyerson (M)
Christopher Benz (C)
Joshua M Stuart (JM)

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests 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.

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Auteurs

Jian Carrot-Zhang (J)

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.

Nyasha Chambwe (N)

Institute for Systems Biology, Seattle, WA 98109, USA.

Jeffrey S Damrauer (JS)

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Theo A Knijnenburg (TA)

Institute for Systems Biology, Seattle, WA 98109, USA.

A Gordon Robertson (AG)

British Columbia Cancer Agency, Genome Sciences Centre, Vancouver, BC V5Z4S6, Canada.

Christina Yau (C)

Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, USA.

Wanding Zhou (W)

Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Ashton C Berger (AC)

The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Kuan-Lin Huang (KL)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Justin Y Newberg (JY)

Foundation Medicine, Cambridge, MA 02141, USA.

R Jay Mashl (RJ)

Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.

Alessandro Romanel (A)

Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo (Trento), Italy.

Rosalyn W Sayaman (RW)

Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.

Francesca Demichelis (F)

Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Povo (Trento), Italy.

Ina Felau (I)

National Cancer Institute, Bethesda, MD 20892, USA.

Garrett M Frampton (GM)

Foundation Medicine, Cambridge, MA 02141, USA.

Seunghun Han (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.

Katherine A Hoadley (KA)

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Anab Kemal (A)

National Cancer Institute, Bethesda, MD 20892, USA.

Peter W Laird (PW)

Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Alexander J Lazar (AJ)

Departments of Pathology, Genomic Medicine, and Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Xiuning Le (X)

Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Ninad Oak (N)

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Hui Shen (H)

Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Christopher K Wong (CK)

UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

Jean C Zenklusen (JC)

National Cancer Institute, Bethesda, MD 20892, USA.

Elad Ziv (E)

Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.

Andrew D Cherniack (AD)

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. Electronic address: achernia@broadinstitute.org.

Rameen Beroukhim (R)

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; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: rameen_beroukhim@dfci.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Caractéristiques de la population › Ethnies › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › Protéine-7 contenant une boite F et des répétitions WD › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génétique des populations › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome humain › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Séquençage nucléotidique à haut débit › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Tumeurs › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Comprehensive Analysis of Genetic Ancestry and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéine Von Hippel-Lindau supresseur de tumeur › Comprehensive Analysis of Genetic Ancestry and...