Show simple item record

dc.contributor.authorCastro, Mauro AAen
dc.contributor.authorde, Santiago Inesen
dc.contributor.authorCampbell, Thomasen
dc.contributor.authorVaughn, Courtneyen
dc.contributor.authorHickey, Theresa Een
dc.contributor.authorRoss, Edithen
dc.contributor.authorTilley, Wayne Den
dc.contributor.authorMarkowetz, Florianen
dc.contributor.authorPonder, Bruceen
dc.contributor.authorMeyer, Kerstinen
dc.date.accessioned2015-11-11T12:53:35Z
dc.date.available2015-11-11T12:53:35Z
dc.date.issued2015-11-30en
dc.identifier.citationNature Genetics 2016, 48: 12-21. doi:10.1038/ng.3458en
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252583
dc.description.abstractGenetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network between transcription factors (TFs) and putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via eQTLs. We identified 36 overlapping regulons that were enriched and formed a distinct cluster within the network, suggesting shared biology. The risk-TFs driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to ER⁺ luminal A/B and to ER⁻ basal-like cancers and to different, luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation to reveal the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.
dc.description.sponsorshipThis work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNPG
dc.titleRegulators of genetic risk of breast cancer identified by integrative network analysisen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.3458en
prism.endingPage21
prism.publicationDate2015en
prism.publicationNameNature Geneticsen
prism.startingPage12
prism.volume48en
dc.rioxxterms.funderCRUK
dcterms.dateAccepted2015-11-06en
rioxxterms.versionofrecord10.1038/ng.3458en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-11-30en
dc.contributor.orcidMarkowetz, Florian [0000-0002-2784-5308]
dc.contributor.orcidMeyer, Kerstin [0000-0001-5906-1498]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
pubs.funder-project-idCancer Research UK (CB4320)
rioxxterms.freetoread.startdate2016-05-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record