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dc.contributor.authorNaidoo, K
dc.contributor.authorWai, PT
dc.contributor.authorMaguire, SL
dc.contributor.authorDaley, F
dc.contributor.authorHaider, S
dc.contributor.authorKriplani, D
dc.contributor.authorCampbell, J
dc.contributor.authorMirza, H
dc.contributor.authorGrigoriadis, A
dc.contributor.authorTutt, A
dc.contributor.authorMoseley, PM
dc.contributor.authorAbdel-Fatah, TMA
dc.contributor.authorChan, SYT
dc.contributor.authorMadhusudan, S
dc.contributor.authorRhaka, EA
dc.contributor.authorEllis, IO
dc.contributor.authorLord, CJ
dc.contributor.authorYuan, Y
dc.contributor.authorGreen, AR
dc.contributor.authorNatrajan, R
dc.date.accessioned2017-10-16T10:32:53Z
dc.date.issued2018-01-01
dc.identifier.citationMolecular cancer therapeutics, 2018, 17 (1), pp. 306 - 315
dc.identifier.issn1535-7163
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/849
dc.identifier.eissn1538-8514
dc.identifier.doi10.1158/1535-7163.mct-17-0760
dc.description.abstractDisruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. We therefore aimed to assess the frequency and distribution of CDK12 protein expression by IHC in independent cohorts of breast cancer and correlate this with outcome and genomic status. We found that 21% of primary unselected breast cancers were CDK12 high, and 10.5% were absent, by IHC. CDK12 positivity correlated with HER2 positivity but was not an independent predictor of breast cancer-specific survival taking HER2 status into account; however, absent CDK12 protein expression significantly correlated with a triple-negative phenotype. Interestingly, CDK12 protein absence was associated with reduced expression of a number of DDR proteins including ATR, Ku70/Ku80, PARP1, DNA-PK, and γH2AX, suggesting a novel mechanism of CDK12-associated DDR dysregulation in breast cancer. Our data suggest that diagnostic IHC quantification of CDK12 in breast cancer is feasible, with CDK12 absence possibly signifying defective DDR function. This may have important therapeutic implications, particularly for triple-negative breast cancers. Mol Cancer Ther; 17(1); 306-15. ©2017 AACR.
dc.formatPrint-Electronic
dc.format.extent306 - 315
dc.languageeng
dc.language.isoeng
dc.publisherAMER ASSOC CANCER RESEARCH
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectDNA Damage
dc.subjectCyclin-Dependent Kinases
dc.subjectImmunohistochemistry
dc.subjectRetrospective Studies
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectBiomarkers, Tumor
dc.titleEvaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-10-19
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1158/1535-7163.mct-17-0760
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular cancer therapeutics
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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Target Validation and DNA Damage Response
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Target Validation and DNA Damage Response
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume17
pubs.embargo.termsNot known
icr.researchteamTarget Validation and DNA Damage Response
icr.researchteamComputational Pathology & Integrated Genomics
icr.researchteamFunctional Genomics
icr.researchteamGene Function
dc.contributor.icrauthorNaidoo, Kalnisha
dc.contributor.icrauthorHaider, Syed
dc.contributor.icrauthorCampbell, James
dc.contributor.icrauthorTutt, Andrew
dc.contributor.icrauthorLord, Christopher
dc.contributor.icrauthorYuan, Yinyin
dc.contributor.icrauthorNatrajan, Rachael


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