Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
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Author
Zhang, Xiaoyang
Francis, Joshua M.
Imielinski, Marcin
Watanabe, Hideo
Cherniack, Andrew D.
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https://doi.org/10.1038/ng.3470Metadata
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Zhang, Xiaoyang, Peter S. Choi, Joshua M. Francis, Marcin Imielinski, Hideo Watanabe, Andrew D. Cherniack, and Matthew Meyerson. 2016. “Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers.” Nature genetics 48 (2): 176-182. doi:10.1038/ng.3470. http://dx.doi.org/10.1038/ng.3470.Abstract
Whole genome analysis approaches are revealing recurrent cancer-associated somatic alterations in non-coding DNA regions. We combined somatic copy number analysis of 12 tumor types with tissue-specific epigenetic profiling to identify significant regions of focal amplification harboring super-enhancers. Copy-number gains of non-coding regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC are associated with over-expression of these cancer-related genes. We show that two distinct focal amplifications of super-enhancers 3′ to MYC in lung adenocarcinoma (MYC-LASE) and endometrial carcinoma (MYC-ECSE), are physically associated with the MYC promoter and correlate with MYC over-expression. CRISPR/Cas9-mediated repression or deletion of a constituent enhancer within the MYC-LASE region led to significant reductions in the expression of MYC and its target genes, and to the impairment of anchorage-independent and clonogenic growth, consistent with an oncogenic function. Our results demonstrate that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857881/pdf/Terms of Use
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