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

Wei Cao; Hayan Lee; Wei Wu; Aubhishek Zaman; Sean McCorkle; Ming Yan; Justin Chen; Qinghe Xing; Nasa Sinnott-Armstrong; Hongen Xu; M. Reza Sailani; Wenxue Tang; Yuanbo Cui; Jia liu; Hongyan Guan; Pengju Lv; Xiaoyan Sun; Lei Sun; Pengli Han; Yanan Lou; Jing Chang; Jinwu Wang; Yuchi Gao; Jiancheng Guo; Gundolf Schenk; Alan Hunter Shain; Fred G. Biddle; Eric Collisson; Michael Snyder; Trever G. Bivona

doi:10.1038/s41467-020-17227-z

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

Wei Cao, Hayan Lee, Wei Wu, Aubhishek Zaman, Sean McCorkle, Ming Yan, Justin Chen, Qinghe Xing, Nasa Sinnott-Armstrong, Hongen Xu, M. Reza Sailani, Wenxue Tang, Yuanbo Cui, Jia liu, Hongyan Guan, Pengju Lv, Xiaoyan Sun, Lei Sun, Pengli Han, Yanan LouJing Chang, Jinwu Wang, Yuchi Gao, Jiancheng Guo, Gundolf Schenk, Alan Hunter Shain, Fred G. Biddle, Eric Collisson, Michael Snyder, Trever G. Bivona

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

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.

Original language	English
Article number	3675
Pages (from-to)	3675
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17227-z
State	Published - Jul 22 2020

Keywords

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

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Cao, W., Lee, H., Wu, W., Zaman, A., McCorkle, S., Yan, M., Chen, J., Xing, Q., Sinnott-Armstrong, N., Xu, H., Reza Sailani, M., Tang, W., Cui, Y., liu, J., Guan, H., Lv, P., Sun, X., Sun, L., Han, P., ... Bivona, T. G. (2020). Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma. Nature Communications, 11(1), 3675. Article 3675. https://doi.org/10.1038/s41467-020-17227-z

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title = "Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma",

abstract = "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.",

keywords = "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",

author = "Wei Cao and Hayan Lee and Wei Wu and Aubhishek Zaman and Sean McCorkle and Ming Yan and Justin Chen and Qinghe Xing and Nasa Sinnott-Armstrong and Hongen Xu and {Reza Sailani}, M. and Wenxue Tang and Yuanbo Cui and Jia liu and Hongyan Guan and Pengju Lv and Xiaoyan Sun and Lei Sun and Pengli Han and Yanan Lou and Jing Chang and Jinwu Wang and Yuchi Gao and Jiancheng Guo and Gundolf Schenk and Shain, {Alan Hunter} and Biddle, {Fred G.} and Eric Collisson and Michael Snyder and Bivona, {Trever G.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = jul,

day = "22",

doi = "10.1038/s41467-020-17227-z",

language = "English",

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Cao, W, Lee, H, Wu, W, Zaman, A, McCorkle, S, Yan, M, Chen, J, Xing, Q, Sinnott-Armstrong, N, Xu, H, Reza Sailani, M, Tang, W, Cui, Y, liu, J, Guan, H, Lv, P, Sun, X, Sun, L, Han, P, Lou, Y, Chang, J, Wang, J, Gao, Y, Guo, J, Schenk, G, Shain, AH, Biddle, FG, Collisson, E, Snyder, M & Bivona, TG 2020, 'Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma', Nature Communications, vol. 11, no. 1, 3675, pp. 3675. https://doi.org/10.1038/s41467-020-17227-z

TY - JOUR

T1 - Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma

AU - Cao, Wei

AU - Lee, Hayan

AU - Wu, Wei

AU - Zaman, Aubhishek

AU - McCorkle, Sean

AU - Yan, Ming

AU - Chen, Justin

AU - Xing, Qinghe

AU - Sinnott-Armstrong, Nasa

AU - Xu, Hongen

AU - Reza Sailani, M.

AU - Tang, Wenxue

AU - Cui, Yuanbo

AU - liu, Jia

AU - Guan, Hongyan

AU - Lv, Pengju

AU - Sun, Xiaoyan

AU - Sun, Lei

AU - Han, Pengli

AU - Lou, Yanan

AU - Chang, Jing

AU - Wang, Jinwu

AU - Gao, Yuchi

AU - Guo, Jiancheng

AU - Schenk, Gundolf

AU - Shain, Alan Hunter

AU - Biddle, Fred G.

AU - Collisson, Eric

AU - Snyder, Michael

AU - Bivona, Trever G.

PY - 2020/7/22

Y1 - 2020/7/22

N2 - 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.

AB - 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.

KW - Aged

KW - Biomarkers, Tumor/genetics

KW - Cell Line, Tumor

KW - Chromatin Immunoprecipitation Sequencing

KW - Cohort Studies

KW - CpG Islands

KW - DNA Methylation

KW - Datasets as Topic

KW - Epigenesis, Genetic

KW - Esophageal Neoplasms/genetics

KW - Esophageal Squamous Cell Carcinoma/genetics

KW - Esophagectomy

KW - Esophagus/pathology

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Genomics

KW - Heterochromatin/metabolism

KW - Histones/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Promoter Regions, Genetic/genetics

KW - Proteomics

KW - RNA-Seq

KW - Whole Genome Sequencing

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U2 - 10.1038/s41467-020-17227-z

DO - 10.1038/s41467-020-17227-z

M3 - Article

C2 - 32699215

SN - 2041-1723

VL - 11

SP - 3675

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3675

ER -

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

Abstract

Keywords

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