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

Author

Listed:
  • Wei Cao

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Hayan Lee

    (School of Medicine)

  • Wei Wu

    (University of California San Francisco
    University of California San Francisco)

  • Aubhishek Zaman

    (University of California San Francisco
    University of California San Francisco)

  • Sean McCorkle

    (Brookhaven National Laboratory)

  • Ming Yan

    (Zhengzhou University)

  • Justin Chen

    (School of Medicine)

  • Qinghe Xing

    (Fudan University)

  • Nasa Sinnott-Armstrong

    (School of Medicine)

  • Hongen Xu

    (Zhengzhou University)

  • M. Reza Sailani

    (School of Medicine)

  • Wenxue Tang

    (Zhengzhou University)

  • Yuanbo Cui

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Jia liu

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Hongyan Guan

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Pengju Lv

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Xiaoyan Sun

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Lei Sun

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Pengli Han

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Yanan Lou

    (Zhengzhou Central Hospital Affiliated Zhengzhou University)

  • Jing Chang

    (Jiangsu Mai Jian Biotechnology Development Company)

  • Jinwu Wang

    (Linzhou Cancer Hospital)

  • Yuchi Gao

    (Annoroad Gene Company)

  • Jiancheng Guo

    (Zhengzhou University)

  • Gundolf Schenk

    (University of California San Francisco)

  • Alan Hunter Shain

    (University of California San Francisco)

  • Fred G. Biddle

    (University of Calgary)

  • Eric Collisson

    (University of California San Francisco
    University of California San Francisco)

  • Michael Snyder

    (School of Medicine)

  • Trever G. Bivona

    (University of California San Francisco
    University of California San Francisco)

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.

Suggested Citation

  • 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 & Hong, 2020. "Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17227-z
    DOI: 10.1038/s41467-020-17227-z
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