The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
Open accessAbstract
Whole-genome analysis approaches are identifying recurrent cancer-associated somatic alterations in noncoding 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 noncoding regions harboring super-enhancers near KLF5, USP12, PARD6B and MYC are associated with overexpression 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 overexpression. 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 suggest that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types.
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Self-citationIntegrative analysis of 111 reference human epigenomes
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Self-citationComprehensive genomic characterization of squamous cell lung cancers
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CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
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“…functional role of the amplified e3 enhancer region, we first targeted catalytically inactive Cas9 (dCas9) fused to the Kruppel-associated box (KRAB) transcriptional repressor domain 42,43 to inhibit e3 enhancer activity in NCI-H2009 lung adenocarcinoma cells that contain four copies of MYC-LASE.”
Super-enhancers in the control of cell identity and disease
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Cited by
Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas
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Self-citationSystematic mapping of functional enhancer–promoter connections with CRISPR interference
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Discovery of common and rare genetic risk variants for colorectal cancer
Huyghe, J. R., Bien, S. A., Harrison, T. A., Kang, H. M., Chen, S., Schmit, S. L., Conti, D. V., Qu, C., Jeon, J., Edlund, C. K., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0286-6 · Cited by 544
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
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“…to trans-locations in lymphoma (Bahram et al., 2000; Hemann et al., 2005); (2) mutation or rare amplification of distal enhancers (Sur et al., 2012; Zhang et al., 2016); and (3) activating mutations in signal transduction pathways (e.g., Wnt, Notch) that augment MYC expression (Herranz et al.,…”
Self-citationPromoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element
Cho, S. W., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y. G., Yost, K. E., Kim, J., He, J., Nevins, S. A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.068 · Cited by 459
Metadata
- Authors
- Zhang, X., Choi, P. S., Francis, J. M., Imielinski, M., Watanabe, H., Cherniack, A. D., & Meyerson, M.
- Venue
- Nature Genetics
- Published
- 2015-12-14
- Volume
- 48
- Issue
- 2
- Pages
- 176-182
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2224894504
- Cited by
- 348
- References
- 27
- FWCI
- 13.64
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, X., Choi, P. S., Francis, J. M., Imielinski, M., Watanabe, H., Cherniack, A. D., & Meyerson, M. (2016). Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nature Genetics. https://doi.org/10.1038/ng.3470
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