Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.
Wei CaoHayan LeeWei WuAubhishek ZamanSean McCorkleMing YanJustin ChenQinghe XingNicholas A Sinnott-ArmstrongHongen XuM Reza SailaniWenxue TangYuanbo CuiJia LiuHongyan GuanPengju LvXiaoyan SunLei SunPengli HanYanan LouJing ChangJinwu WangYuchi GaoJiancheng GuoGundolf SchenkAlan Hunter ShainFred G BiddleEric CollissonMichael Paul SnyderTrever G BivonaPublished in: Nature communications (2020)
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.
Keyphrases
- dna methylation
- gene expression
- genome wide
- papillary thyroid
- high resolution
- copy number
- squamous cell
- cell proliferation
- long non coding rna
- stem cells
- single cell
- small molecule
- childhood cancer
- high throughput
- lymph node metastasis
- squamous cell carcinoma
- binding protein
- young adults
- amino acid
- risk assessment
- dna binding
- cell migration