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Title: Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity
Authors: Ooi, W.F
Xing, M
Xu, C 
Yao, X
Ramlee, M.K
Lim, M.C 
Cao, F 
Lim, K 
Babu, D 
Poon, L.-F 
Lin Suling, J
Qamra, A 
Irwanto, A
Qu Zhengzhong, J
Nandi, T
Lee-Lim, A.P
Chan, Y.S
Tay, S.T 
Lee, M.H 
Davies, J.O.J
Wong, W.K
Soo, K.C 
Chan, W.H 
Ong, H.S 
Chow, P 
Wong, C.Y 
Rha, S.Y
Liu, J
Hillmer, A.M
Hughes, J.R
Rozen, S 
Teh, B.T 
Fullwood, M.J 
Li, S 
Tan, P 
Keywords: hepatocyte nuclear factor 4alpha
transcription factor Cdx2
cells and cell components
gene expression
genetic analysis
cancer susceptibility
cell interaction
controlled study
enhancer region
gene expression
genetic heterogeneity
genetic risk
histone modification
human cell
human tissue
primary tumor
single nucleotide polymorphism
stomach adenocarcinoma
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Ooi, W.F, Xing, M, Xu, C, Yao, X, Ramlee, M.K, Lim, M.C, Cao, F, Lim, K, Babu, D, Poon, L.-F, Lin Suling, J, Qamra, A, Irwanto, A, Qu Zhengzhong, J, Nandi, T, Lee-Lim, A.P, Chan, Y.S, Tay, S.T, Lee, M.H, Davies, J.O.J, Wong, W.K, Soo, K.C, Chan, W.H, Ong, H.S, Chow, P, Wong, C.Y, Rha, S.Y, Liu, J, Hillmer, A.M, Hughes, J.R, Rozen, S, Teh, B.T, Fullwood, M.J, Li, S, Tan, P (2016). Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. Nature Communications 7 : 12983. ScholarBank@NUS Repository.
Abstract: 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 HNF4?. 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. © 2016 The Author(s).
Source Title: Nature Communications
ISSN: 20411723
DOI: 10.1038/ncomms12983
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