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

Nature Communications
W CaoTrever G. Bivona

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.

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Citations

Sep 22, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yuanbo CuiFangxia Guan

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Methods Mentioned

BETA
WGBS
methylation profiling
RNAseq
immunoprecipitation
RNA-seq
PCR
pull-down
ChIP-seq
xenograft
electrophoresis

Software Mentioned

RNAseq
Sambamba
SciPy
BWA package
CNVkit
MetaSV
[UNK] Real - Time PCR System
MatLab
MuTect2
Illumina Bcl2fastq

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