Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.

Aged Biomarkers, Tumor / genetics Cell Line, Tumor Chromatin Immunoprecipitation Sequencing Cohort Studies CpG Islands DNA Methylation Datasets as Topic Epigenesis, Genetic Esophageal Neoplasms / genetics Esophageal Squamous Cell Carcinoma / genetics Esophagectomy Esophagus / pathology Female Gene Expression Regulation, Neoplastic Genomics Heterochromatin / metabolism Histones / genetics Humans Male Middle Aged Promoter Regions, Genetic / genetics Proteomics RNA-Seq Whole Genome Sequencing

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
22 07 2020
Historique:
received: 20 12 2019
accepted: 17 06 2020
entrez: 24 7 2020
pubmed: 24 7 2020
medline: 10 9 2020
Statut: epublish

Résumé

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery.

Identifiants

DOI: 10.1038/s41467-020-17227-z PMID: 32699215 PMC: PMC7376194
pubmed: 32699215
doi: 10.1038/s41467-020-17227-z
pii: 10.1038/s41467-020-17227-z
pmc: PMC7376194
doi:

Substances chimiques

Biomarkers, Tumor 0
Heterochromatin 0
Histones 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

3675

Subventions

Organisme : NCI NIH HHS
ID : R01 CA230263
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169338
Pays : United States
Organisme : NCI NIH HHS
ID : K22 CA217997
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211052
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204302
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227807
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA222862
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA178015
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217882
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224081
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239604
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210974
Pays : United States
Organisme : NIH HHS
ID : S10 OD020141
Pays : United States

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Auteurs

Wei Cao (W)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China. caowei7@zzu.edu.cn.
ORCID: 0000-0002-2851-4359

Hayan Lee (H)

Department of Genetics, School of Medicine, Stanford University, CA, USA.
ORCID: 0000-0003-0571-3192

Wei Wu (W)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA. wei.wu@ucsf.edu.
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. wei.wu@ucsf.edu.
ORCID: 0000-0002-6556-067X

Aubhishek Zaman (A)

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

Sean McCorkle (S)

Computational Science Initiative, Brookhaven National Laboratory, Upton, NY, USA.

Ming Yan (M)

Basic Medical College, Zhengzhou University, Zhengzhou, China.

Justin Chen (J)

Department of Genetics, School of Medicine, Stanford University, CA, USA.

Qinghe Xing (Q)

Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, China.

Nasa Sinnott-Armstrong (N)

Department of Genetics, School of Medicine, Stanford University, CA, USA.
ORCID: 0000-0003-4490-0601

Hongen Xu (H)

Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

M Reza Sailani (MR)

Department of Genetics, School of Medicine, Stanford University, CA, USA.

Wenxue Tang (W)

Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

Yuanbo Cui (Y)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Jia Liu (J)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Hongyan Guan (H)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Pengju Lv (P)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Xiaoyan Sun (X)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Lei Sun (L)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Pengli Han (P)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Yanan Lou (Y)

Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.

Jing Chang (J)

Jiangsu Mai Jian Biotechnology Development Company, Wuxi, China.

Jinwu Wang (J)

Department of Pathology, Linzhou Cancer Hospital, Linzhou, China.

Yuchi Gao (Y)

Annoroad Gene Company, Beijing, China.

Jiancheng Guo (J)

Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.

Gundolf Schenk (G)

Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA.
ORCID: 0000-0003-1240-9949

Alan Hunter Shain (AH)

Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.

Fred G Biddle (FG)

Department of Biological Sciences, University of Calgary, Calgary, Canada.

Eric Collisson (E)

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

Michael Snyder (M)

Department of Genetics, School of Medicine, Stanford University, CA, USA. mpsnyder@stanford.edu.
ORCID: 0000-0003-0784-7987

Trever G Bivona (TG)

Department of Medicine, University of California San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.
ORCID: 0000-0001-5734-4128

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunoprécipitation › Immunoprécipitation de la chromatine › Séquençage après immunoprécipitation de la chromatine › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Ilots CpG › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Jeux de données comme sujet › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Tumeurs gastro-intestinales › Tumeurs de l'oesophage › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Tumeurs gastro-intestinales › Tumeurs de l'oesophage › Carcinome épidermoïde de l'oesophage › Multi-faceted epigenetic dysregulation of gene...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie digestive › Oesophagectomie › Multi-faceted epigenetic dysregulation of gene...
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