Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity

Wen Fong Ooi, Manjie Xing, Chang Xu, Xiaosai Yao, Muhammad Khairul Ramlee, Mei Chee Lim, Fan Cao, Kevin Lim, Deepak Babu, Lai Fong Poon, Joyce Lin Suling, Aditi Qamra, Astrid Irwanto, James Qu Zhengzhong, Tannistha Nandi, Ai Ping Lee-Lim, Yang Sun Chan, Su Ting Tay, Ming Hui Lee, James O.J. Davies & 15 others Wai Keong Wong, Khee Chee Soo, Weng Hoong Chan, Hock Soo Ong, Pierce Chow, Chow Yin Wong, SunYoung Rha, Jianjun Liu, Axel M. Hillmer, Jim R. Hughes, Steve Rozen, Bin Tean Teh, Melissa Jane Fullwood, Shang Li, Patrick Tan

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 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.

Original languageEnglish
Article number12983
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 Sep 28

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chromatin
cultured cells
Epigenomics
Chromatin
Stomach
Adenocarcinoma
cancer
oncogenes
genome
mortality
gene expression
Hepatocyte Nuclear Factor 4
profiles
Gene expression
Tumors
Cell Line
Neoplasms
Transcription Factors
tumors
Genes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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, [12983]. https://doi.org/10.1038/ncomms12983
Ooi, Wen Fong ; Xing, Manjie ; Xu, Chang ; Yao, Xiaosai ; Ramlee, Muhammad Khairul ; Lim, Mei Chee ; Cao, Fan ; Lim, Kevin ; Babu, Deepak ; Poon, Lai Fong ; Lin Suling, Joyce ; Qamra, Aditi ; Irwanto, Astrid ; Qu Zhengzhong, James ; Nandi, Tannistha ; Lee-Lim, Ai Ping ; Chan, Yang Sun ; Tay, Su Ting ; Lee, Ming Hui ; Davies, James O.J. ; Wong, Wai Keong ; Soo, Khee Chee ; Chan, Weng Hoong ; Ong, Hock Soo ; Chow, Pierce ; Wong, Chow Yin ; Rha, SunYoung ; Liu, Jianjun ; Hillmer, Axel M. ; Hughes, Jim R. ; Rozen, Steve ; Teh, Bin Tean ; Fullwood, Melissa Jane ; Li, Shang ; Tan, Patrick. / Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. In: Nature communications. 2016 ; Vol. 7.
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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 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, WF, Xing, M, Xu, C, Yao, X, Ramlee, MK, Lim, MC, Cao, F, Lim, K, Babu, D, Poon, LF, Lin Suling, J, Qamra, A, Irwanto, A, Qu Zhengzhong, J, Nandi, T, Lee-Lim, AP, Chan, YS, Tay, ST, Lee, MH, Davies, JOJ, Wong, WK, Soo, KC, Chan, WH, Ong, HS, Chow, P, Wong, CY, Rha, S, Liu, J, Hillmer, AM, Hughes, JR, Rozen, S, Teh, BT, Fullwood, MJ, Li, S & Tan, P 2016, 'Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity', Nature communications, vol. 7, 12983. https://doi.org/10.1038/ncomms12983

Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity. / Ooi, Wen Fong; Xing, Manjie; Xu, Chang; Yao, Xiaosai; Ramlee, Muhammad Khairul; Lim, Mei Chee; Cao, Fan; Lim, Kevin; Babu, Deepak; Poon, Lai Fong; Lin Suling, Joyce; Qamra, Aditi; Irwanto, Astrid; Qu Zhengzhong, James; Nandi, Tannistha; Lee-Lim, Ai Ping; Chan, Yang Sun; Tay, Su Ting; Lee, Ming Hui; Davies, James O.J.; Wong, Wai Keong; Soo, Khee Chee; Chan, Weng Hoong; Ong, Hock Soo; Chow, Pierce; Wong, Chow Yin; Rha, SunYoung; Liu, Jianjun; Hillmer, Axel M.; Hughes, Jim R.; Rozen, Steve; Teh, Bin Tean; Fullwood, Melissa Jane; Li, Shang; Tan, Patrick.

In: Nature communications, Vol. 7, 12983, 28.09.2016.

Research output: Contribution to journalArticle

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AU - Xing, Manjie

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AU - Lim, Mei Chee

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AU - Lim, Kevin

AU - Babu, Deepak

AU - Poon, Lai Fong

AU - Lin Suling, Joyce

AU - Qamra, Aditi

AU - Irwanto, Astrid

AU - Qu Zhengzhong, James

AU - Nandi, Tannistha

AU - Lee-Lim, Ai Ping

AU - Chan, Yang Sun

AU - Tay, Su Ting

AU - Lee, Ming Hui

AU - Davies, James O.J.

AU - Wong, Wai Keong

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AU - Chan, Weng Hoong

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AU - Chow, Pierce

AU - Wong, Chow Yin

AU - Rha, SunYoung

AU - Liu, Jianjun

AU - Hillmer, Axel M.

AU - Hughes, Jim R.

AU - Rozen, Steve

AU - Teh, Bin Tean

AU - Fullwood, Melissa Jane

AU - Li, Shang

AU - Tan, Patrick

PY - 2016/9/28

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N2 - 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.

AB - 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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