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dc.contributor.authorGriffith, OLen_US
dc.contributor.authorSpies, NCen_US
dc.contributor.authorAnurag, Men_US
dc.contributor.authorGriffith, Men_US
dc.contributor.authorLuo, Jen_US
dc.contributor.authorTu, Den_US
dc.contributor.authorYeo, Ben_US
dc.contributor.authorKunisaki, Jen_US
dc.contributor.authorMiller, CAen_US
dc.contributor.authorKrysiak, Ken_US
dc.contributor.authorHundal, Jen_US
dc.contributor.authorAinscough, BJen_US
dc.contributor.authorSkidmore, ZLen_US
dc.contributor.authorCampbell, Ken_US
dc.contributor.authorKumar, Ren_US
dc.contributor.authorFronick, Cen_US
dc.contributor.authorCook, Len_US
dc.contributor.authorSnider, JEen_US
dc.contributor.authorDavies, Sen_US
dc.contributor.authorKavuri, SMen_US
dc.contributor.authorChang, ECen_US
dc.contributor.authorMagrini, Ven_US
dc.contributor.authorLarson, DEen_US
dc.contributor.authorFulton, RSen_US
dc.contributor.authorLiu, Sen_US
dc.contributor.authorLeung, Sen_US
dc.contributor.authorVoduc, Den_US
dc.contributor.authorBose, Ren_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorWilson, RKen_US
dc.contributor.authorNielsen, TOen_US
dc.contributor.authorMardis, ERen_US
dc.contributor.authorEllis, MJen_US
dc.date.accessioned2018-06-07T08:38:53Z
dc.date.accessioned2019-08-07T11:36:55Z
dc.date.issued2018-09-04en_US
dc.identifier.citationNature communications, 2018, 9 (1), pp. 3476 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3311
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-018-05914-xen_US
dc.description.abstractHere we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.en_US
dc.formatElectronicen_US
dc.format.extent3476 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1752
dc.relation.replacesinternal/1752
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHumansen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectMAP Kinase Kinase Kinase 1en_US
dc.subjectNeurofibromin 1en_US
dc.subjectReceptors, Estrogenen_US
dc.subjectPrognosisen_US
dc.subjectSurvival Analysisen_US
dc.subjectCase-Control Studiesen_US
dc.subjectCohort Studiesen_US
dc.subjectPostmenopauseen_US
dc.subjectMutationen_US
dc.subjectAdulten_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectPhosphatidylinositol 3-Kinasesen_US
dc.subjectClass I Phosphatidylinositol 3-Kinasesen_US
dc.subjectDiscoidin Domain Receptor 1en_US
dc.titleThe prognostic effects of somatic mutations in ER-positive breast cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-07-05en_US
rioxxterms.versionofrecord10.1038/s41467-018-05914-xen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2018-09-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.publication-statusPublisheden_US
pubs.volume9en_US
pubs.embargo.termsNot knownen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen_US


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