Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity
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, n...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2016
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| _version_ | 1826293425981358080 |
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| author | Ooi, W Xing, M Xu, C Yao, X Ramlee, M Lim, M Cao, F Lim, K Babu, D Poon, L Lin Suling, J Qamra, A Irwanto, A Qu Zhengzhong, J Nandi, T Lee-Lim, A Chan, Y Tay, S Lee, M Davies, J Wong, W Soo, K Chan, W Ong, H Chow, P Wong, C Rha, S Liu, J Hillmer, A Hughes, J Rozen, S Teh, B Fullwood, M Li, S Tan, P |
| author_facet | Ooi, W Xing, M Xu, C Yao, X Ramlee, M Lim, M Cao, F Lim, K Babu, D Poon, L Lin Suling, J Qamra, A Irwanto, A Qu Zhengzhong, J Nandi, T Lee-Lim, A Chan, Y Tay, S Lee, M Davies, J Wong, W Soo, K Chan, W Ong, H Chow, P Wong, C Rha, S Liu, J Hillmer, A Hughes, J Rozen, S Teh, B Fullwood, M Li, S Tan, P |
| author_sort | Ooi, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:29:54Z |
| format | Journal article |
| id | oxford-uuid:ba5d2d8c-fa6e-48ab-be90-54c70736637b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:29:54Z |
| publishDate | 2016 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:ba5d2d8c-fa6e-48ab-be90-54c70736637b2022-03-27T05:09:21ZEpigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ba5d2d8c-fa6e-48ab-be90-54c70736637bEnglishSymplectic Elements at OxfordSpringer Nature2016Ooi, WXing, MXu, CYao, XRamlee, MLim, MCao, FLim, KBabu, DPoon, LLin Suling, JQamra, AIrwanto, AQu Zhengzhong, JNandi, TLee-Lim, AChan, YTay, SLee, MDavies, JWong, WSoo, KChan, WOng, HChow, PWong, CRha, SLiu, JHillmer, AHughes, JRozen, STeh, BFullwood, MLi, STan, PRegulatory 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. |
| spellingShingle | Ooi, W Xing, M Xu, C Yao, X Ramlee, M Lim, M Cao, F Lim, K Babu, D Poon, L Lin Suling, J Qamra, A Irwanto, A Qu Zhengzhong, J Nandi, T Lee-Lim, A Chan, Y Tay, S Lee, M Davies, J Wong, W Soo, K Chan, W Ong, H Chow, P Wong, C Rha, S Liu, J Hillmer, A Hughes, J Rozen, S Teh, B Fullwood, M Li, S Tan, P Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title | Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title_full | Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title_fullStr | Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title_full_unstemmed | Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title_short | Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity |
| title_sort | epigenomic profiling of primary gastric adenocarcinoma reveals super enhancer heterogeneity |
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