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Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma
- Publication Year :
- 2019
- Publisher :
- Cold Spring Harbor Laboratory, 2019.
-
Abstract
- Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome and two-thirds occur in long non-coding (lnc)RNA regions. DNA methylation and epigenetic heterogeneity both coincide with chromosomal topological alterations. Gene body methylation, polycomb repressive complex occupancy, and CTCF binding sites associate with cancer-specific gene regulation. Epigenetically-mediated activation of non-canonical WNT signaling and the lncRNAESCCAL-1were validated as potential ESCC driver alterations. Gene-specific cancer driver roles of epigenetic alterations and heterogeneity are identified.
- Subjects :
- Regulation of gene expression
0303 health sciences
Wnt signaling pathway
Cancer
Methylation
Biology
medicine.disease
Genome
03 medical and health sciences
0302 clinical medicine
030220 oncology & carcinogenesis
DNA methylation
medicine
Cancer research
Epigenetics
Gene
030304 developmental biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3bde219cea0153e564cdeecdd79c7184
- Full Text :
- https://doi.org/10.1101/641357