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Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.
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.
Afiliação
  • Cao W; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China. caowei7@zzu.edu.cn.
  • Lee H; Department of Genetics, School of Medicine, Stanford University, CA, USA.
  • Wu W; Department of Medicine, University of California San Francisco, San Francisco, CA, USA. wei.wu@ucsf.edu.
  • Zaman A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. wei.wu@ucsf.edu.
  • McCorkle S; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Yan M; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Chen J; Computational Science Initiative, Brookhaven National Laboratory, Upton, NY, USA.
  • Xing Q; Basic Medical College, Zhengzhou University, Zhengzhou, China.
  • Sinnott-Armstrong N; Department of Genetics, School of Medicine, Stanford University, CA, USA.
  • Xu H; Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai, China.
  • Sailani MR; Department of Genetics, School of Medicine, Stanford University, CA, USA.
  • Tang W; Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Cui Y; Department of Genetics, School of Medicine, Stanford University, CA, USA.
  • Liu J; Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Guan H; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Lv P; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Sun X; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Sun L; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Han P; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Lou Y; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Chang J; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Wang J; Translational Medical Center, Zhengzhou Central Hospital Affiliated Zhengzhou University, Zhengzhou, China.
  • Gao Y; Jiangsu Mai Jian Biotechnology Development Company, Wuxi, China.
  • Guo J; Department of Pathology, Linzhou Cancer Hospital, Linzhou, China.
  • Schenk G; Annoroad Gene Company, Beijing, China.
  • Shain AH; Precision Medicine Center, The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Biddle FG; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA.
  • Collisson E; Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
  • Snyder M; Department of Biological Sciences, University of Calgary, Calgary, Canada.
  • Bivona TG; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Nat Commun ; 11(1): 3675, 2020 07 22.
Article em En | MEDLINE | ID: mdl-32699215
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/ß-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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Epigênese Genética / Carcinoma de Células Escamosas do Esôfago Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Esofágicas / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Epigênese Genética / Carcinoma de Células Escamosas do Esôfago Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article