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dc.contributor.authorMartin, L-A
dc.contributor.authorRibas, R
dc.contributor.authorSimigdala, N
dc.contributor.authorSchuster, E
dc.contributor.authorPancholi, S
dc.contributor.authorTenev, T
dc.contributor.authorGellert, P
dc.contributor.authorBuluwela, L
dc.contributor.authorHarrod, A
dc.contributor.authorThornhill, A
dc.contributor.authorNikitorowicz-Buniak, J
dc.contributor.authorBhamra, A
dc.contributor.authorTurgeon, M-O
dc.contributor.authorPoulogiannis, G
dc.contributor.authorGao, Q
dc.contributor.authorMartins, V
dc.contributor.authorHills, M
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorFribbens, C
dc.contributor.authorPatani, N
dc.contributor.authorLi, Z
dc.contributor.authorSikora, MJ
dc.contributor.authorTurner, N
dc.contributor.authorZwart, W
dc.contributor.authorOesterreich, S
dc.contributor.authorCarroll, J
dc.contributor.authorAli, S
dc.contributor.authorDowsett, M
dc.date.accessioned2017-10-24T10:45:53Z
dc.date.issued2017-11-30
dc.identifier.citationNature communications, 2017, 8 (1), pp. 1865 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/871
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-017-01864-y
dc.description.abstractResistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.
dc.formatElectronic
dc.format.extent1865 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectTamoxifen
dc.subjectEstradiol
dc.subjectSelective Estrogen Receptor Modulators
dc.subjectEstrogen Receptor alpha
dc.subjectDrug Resistance, Neoplasm
dc.subjectMutation
dc.subjectFemale
dc.subjectMCF-7 Cells
dc.subjectEstrogen Receptor Antagonists
dc.subjectFulvestrant
dc.titleDiscovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.
dc.typeJournal Article
dcterms.dateAccepted2017-10-20
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1038/s41467-017-01864-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-11-30
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNot known
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/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
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.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
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/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
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.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamEndocrine Therapy Resistanceen_US
icr.researchteamMolecular Oncologyen_US
icr.researchteamSignalling & Cancer Metabolismen_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorNikitorowicz-Buniak, Joannaen
dc.contributor.icrauthorSchuster, Eugeneen
dc.contributor.icrauthorTurgeon, Marc-Olivieren
dc.contributor.icrauthorMartin, Lesley-Annen
dc.contributor.icrauthorPancholi, Sunilen
dc.contributor.icrauthorPoulogiannis, Georgiosen
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorTurner, Nicholasen
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorGao, Qiongen
dc.contributor.icrauthorMarsden,en


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