Research Papers:

Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer

Xiaoyan Li, Yining Liu, Jiachun Lu and Min Zhao _

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Oncotarget. 2017; 8:91558-91567. https://doi.org/10.18632/oncotarget.21227

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Xiaoyan Li1,*, Yining Liu2,*, Jiachun Lu3 and Min Zhao4

1Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung & Blood Vessel Disease, Beijing, China

2The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China

3The School of Public Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

4School of Engineering, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Queensland, Australia

*These authors have contributed equally to this work

Correspondence to:

Min Zhao, email: [email protected].

Keywords: systems biology, cancer genomics, enhancer, copy number variation

Received: May 31, 2017     Accepted: August 04, 2017     Published: September 23, 2017


Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput sequencing. Enhancers have been associated with malfunctions in cancer development resulting from point mutations in regulatory regions. However, the potential impact of copy number variations (CNVs) on enhancer regions is unknown. To learn more about the relationship between enhancers and cancer, we integrated the CNVs data on enhancers and explored their targeting gene expression pattern in high-grade ovarian cancer. Using human enhancer-gene interaction data with 13,691 interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found that the 2,910 copy number gain events of enhancer are significantly correlated with the up-regulation of targeting genes. We further identified that a number of highly mutated super-enhancers, with concordant gene expression change on their targeting genes. We also identified 18 targeting genes by super-enhancers with prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B. We are the first to report that abundant copy number variations on enhancers could change the expression of their targeting genes which would be valuable for the design of enhancer-based cancer treatment strategy.

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