Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity

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Abstract

© 2016 The Author(s). Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression.

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Ooi, W. F., Xing, M., Xu, C., Yao, X., Ramlee, M. K., Lim, M. C., … Tan, P. (2016). Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. Nature Communications, 7. https://doi.org/10.1038/ncomms12983

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