Show simple item record

dc.contributor.authorde la Rosa, Jorgeen
dc.contributor.authorWeber, Juliaen
dc.contributor.authorFriedrich, Mathias Josefen
dc.contributor.authorLi, Yilongen
dc.contributor.authorRad, Lenaen
dc.contributor.authorPonstingl, Hannesen
dc.contributor.authorLiang, Qien
dc.contributor.authorde Quirós, Sandra Bernaldoen
dc.contributor.authorNoorani, Imranen
dc.contributor.authorMetzakopian, Emmanouilen
dc.contributor.authorStrong, Alexanderen
dc.contributor.authorLi, Amyen
dc.contributor.authorAstudillo, Auroraen
dc.contributor.authorFernández-García, María Teresaen
dc.contributor.authorFernández-García, María Soledaden
dc.contributor.authorHoffman, Gary Jen
dc.contributor.authorFuente, Rocíoen
dc.contributor.authorVassiliou, Georgeen
dc.contributor.authorRad, Rolanden
dc.contributor.authorLópez-Otín, Carlosen
dc.contributor.authorBradley, Allanen
dc.contributor.authorCadiñanos, Juanen
dc.date.accessioned2020-10-27T16:00:09Z
dc.date.available2020-10-27T16:00:09Z
dc.date.issued2017-05-01en
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/312049
dc.description.abstractThe overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer. We validated ZBTB20, CELF2, PARD3, AKAP13 and WAC, which were identified by our screens in multiple cancer types, as new tumor suppressor genes in prostate cancer. We demonstrated their synergy with PTEN in preventing invasion in vitro and confirmed their clinical relevance. Further characterization of Wac in vivo showed obligate haploinsufficiency for this gene (which encodes an autophagy-regulating factor) in a Pten-deficient context. Our study identified complex PTEN-cooperating tumor suppressor networks in different cancer types, with potential clinical implications.
dc.languageengen
dc.rightsAll rights reserved
dc.titleA single-copy Sleeping Beauty transposon mutagenesis screen identifies new PTEN-cooperating tumor suppressor genes.en
dc.typeArticle
prism.issueIdentifier5en
prism.publicationDate2017en
prism.publicationNameNat Geneten
prism.volume49en
dc.identifier.doi10.17863/CAM.59144
dcterms.dateAccepted2017-02-24en
rioxxterms.versionofrecord10.1038/ng.3817en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-05-01en
dc.contributor.orcidPonstingl, Hannes [0000-0001-7573-1703]
dc.contributor.orcidVassiliou, George [0000-0003-4337-8022]
dc.contributor.orcidBradley, Allan [0000-0002-2349-8839]
dc.contributor.orcidCadiñanos, Juan [0000-0001-7561-7759]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_PC_12009)
cam.issuedOnline2017-03-20en
rioxxterms.freetoread.startdate2017-11-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record