Journal article
Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.7MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms12983
Authors
+ Wellcome Trust
More from this funder
- Funding agency for:
- Davies, J
- Funding agency for:
- Hughes, J
- Grant:
- 098931/Z/12/Z
- Grant:
- 106130/Z/14/Z
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 7
- Article number:
- 12983
- Publication date:
- 2016-09-28
- Acceptance date:
- 2016-08-23
- DOI:
- EISSN:
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2041-1723
- Pmid:
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27677335
- Language:
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English
- Pubs id:
-
pubs:647655
- UUID:
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uuid:ba5d2d8c-fa6e-48ab-be90-54c70736637b
- Local pid:
-
pubs:647655
- Source identifiers:
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647655
- Deposit date:
-
2019-02-28
- ARK identifier:
Terms of use
- Copyright holder:
- Ooi et al
- Copyright date:
- 2016
- Notes:
- © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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