File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1038/ng.3650
- Scopus: eid_2-s2.0-84984605112
- PMID: 27571262
- WOS: WOS:000384391600022
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer
Title | Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer |
---|---|
Authors | Bailey, Swneke D.Desai, KinjalKron, Ken J.Mazrooei, ParisaSinnott-Armstrong, Nicholas A.Treloar, Aislinn E.Dowar, MarkThu, Kelsie L.Cescon, David W.Silvester, JenniferYang, S. Y.CindyWu, XuePezo, Rossanna C.Haibe-Kains, BenjaminMak, Tak W.Bedard, Philippe L.Pugh, Trevor J.Sallari, Richard C.Lupien, Mathieu |
Issue Date | 2016 |
Citation | Nature Genetics, 2016, v. 48, n. 10, p. 1260-1266 How to Cite? |
Abstract | © 2016 Nature America, Inc. All rights reserved. Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. |
Persistent Identifier | http://hdl.handle.net/10722/292960 |
ISSN | 2023 Impact Factor: 31.7 2023 SCImago Journal Rankings: 17.300 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Bailey, Swneke D. | - |
dc.contributor.author | Desai, Kinjal | - |
dc.contributor.author | Kron, Ken J. | - |
dc.contributor.author | Mazrooei, Parisa | - |
dc.contributor.author | Sinnott-Armstrong, Nicholas A. | - |
dc.contributor.author | Treloar, Aislinn E. | - |
dc.contributor.author | Dowar, Mark | - |
dc.contributor.author | Thu, Kelsie L. | - |
dc.contributor.author | Cescon, David W. | - |
dc.contributor.author | Silvester, Jennifer | - |
dc.contributor.author | Yang, S. Y.Cindy | - |
dc.contributor.author | Wu, Xue | - |
dc.contributor.author | Pezo, Rossanna C. | - |
dc.contributor.author | Haibe-Kains, Benjamin | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Bedard, Philippe L. | - |
dc.contributor.author | Pugh, Trevor J. | - |
dc.contributor.author | Sallari, Richard C. | - |
dc.contributor.author | Lupien, Mathieu | - |
dc.date.accessioned | 2020-11-17T14:57:35Z | - |
dc.date.available | 2020-11-17T14:57:35Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Nature Genetics, 2016, v. 48, n. 10, p. 1260-1266 | - |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292960 | - |
dc.description.abstract | © 2016 Nature America, Inc. All rights reserved. Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. | - |
dc.language | eng | - |
dc.relation.ispartof | Nature Genetics | - |
dc.title | Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/ng.3650 | - |
dc.identifier.pmid | 27571262 | - |
dc.identifier.pmcid | PMC5042848 | - |
dc.identifier.scopus | eid_2-s2.0-84984605112 | - |
dc.identifier.volume | 48 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 1260 | - |
dc.identifier.epage | 1266 | - |
dc.identifier.eissn | 1546-1718 | - |
dc.identifier.isi | WOS:000384391600022 | - |
dc.identifier.issnl | 1061-4036 | - |