학술논문
Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.
Document Type
article
Author
Cao, Wei; Lee, Hayan; Wu, Wei; Zaman, Aubhishek; McCorkle, Sean; Yan, Ming; Chen, Justin; Xing, Qinghe; Sinnott-Armstrong, Nasa; Xu, Hongen; Sailani, M Reza; Tang, Wenxue; Cui, Yuanbo; Liu, Jia; Guan, Hongyan; Lv, Pengju; Sun, Xiaoyan; Sun, Lei; Han, Pengli; Lou, Yanan; Chang, Jing; Wang, Jinwu; Gao, Yuchi; Guo, Jiancheng; Schenk, Gundolf; Shain, Alan Hunter; Biddle, Fred G; Collisson, Eric; Snyder, Michael; Bivona, Trever G
Source
Nature communications. 11(1)
Subject
Language
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.