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

被引：84

作者：

Cao, Wei ^{[1
]}

Lee, Hayan ^{[2
]}

Wu, Wei ^{[3
,4
]}

Zaman, Aubhishek ^{[3
,4
]}

McCorkle, Sean ^{[5
]}

Yan, Ming ^{[6
]}

Chen, Justin ^{[2
]}

Xing, Qinghe ^{[7
,8
]}

Sinnott-Armstrong, Nasa ^{[2
]}

Xu, Hongen ^{[9
]}

Sailani, M. Reza ^{[2
]}

Tang, Wenxue ^{[9
]}

Cui, Yuanbo ^{[1
]}

Liu, Jia ^{[1
]}

Guan, Hongyan ^{[1
]}

Lv, Pengju ^{[1
]}

Sun, Xiaoyan ^{[1
]}

Sun, Lei ^{[1
]}

Han, Pengli ^{[1
]}

Lou, Yanan ^{[1
]}

Chang, Jing ^{[10
]}

Wang, Jinwu ^{[11
]}

Gao, Yuchi ^{[12
]}

Guo, Jiancheng ^{[9
]}

Schenk, Gundolf ^{[13
]}

Shain, Alan Hunter ^{[14
]}

Biddle, Fred G. ^{[15
]}

Collisson, Eric ^{[3
,4
]}

Snyder, Michael ^{[2
]}

Bivona, Trever G. ^{[3
,4
]}

机构：

[1] Zhengzhou Univ, Zhengzhou Cent Hosp Affiliated, Translat Med Ctr, Zhengzhou, Peoples R China

[2] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[5] Brookhaven Natl Lab, Computat Sci Initiat, Upton, NY 11973 USA

[6] Zhengzhou Univ, Basic Med Coll, Zhengzhou, Peoples R China

[7] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China

[8] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China

[9] Zhengzhou Univ, Acad Med Sci, Precis Med Ctr, Zhengzhou, Peoples R China

[10] Jiangsu Mai Jian Biotechnol Dev Co, Wuxi, Jiangsu, Peoples R China

[11] Linzhou Canc Hosp, Dept Pathol, Linzhou, Peoples R China

[12] Annoroad Gene Co, Beijing, Peoples R China

[13] Univ Calif San Francisco, Bakar Computat Hlth Sci Inst, San Francisco, CA 94143 USA

[14] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA USA

[15] Univ Calgary, Dept Biol Sci, Calgary, AB, Canada

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

中国国家自然科学基金;

关键词：

LONG NONCODING RNA; DNA METHYLATION; GENOMIC CHARACTERIZATION; CANCER; ACCURATE; ENCYCLOPEDIA; MUTATIONS; LANDSCAPE; ALIGNMENT; INVASION;

D O I：

10.1038/s41467-020-17227-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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/beta-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. The epigenetic landscape of esophageal squamous cell carcinoma (ESCC) at genome-wide high resolution is incompletely studied. Here, the authors performed an integrated multi-omics analysis of ESCC and non-tumor tissues to define the genome-wide methylome landscape and epigenetic alterations to uncover oncogenic drivers of ESCC.

引用

页数：19

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