dc.contributor.author | Naidoo, K | |
dc.contributor.author | Wai, PT | |
dc.contributor.author | Maguire, SL | |
dc.contributor.author | Daley, F | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Kriplani, D | |
dc.contributor.author | Campbell, J | |
dc.contributor.author | Mirza, H | |
dc.contributor.author | Grigoriadis, A | |
dc.contributor.author | Tutt, A | |
dc.contributor.author | Moseley, PM | |
dc.contributor.author | Abdel-Fatah, TMA | |
dc.contributor.author | Chan, SYT | |
dc.contributor.author | Madhusudan, S | |
dc.contributor.author | Rhaka, EA | |
dc.contributor.author | Ellis, IO | |
dc.contributor.author | Lord, CJ | |
dc.contributor.author | Yuan, Y | |
dc.contributor.author | Green, AR | |
dc.contributor.author | Natrajan, R | |
dc.date.accessioned | 2017-10-16T10:32:53Z | |
dc.date.issued | 2018-01-01 | |
dc.identifier.citation | Molecular cancer therapeutics, 2018, 17 (1), pp. 306 - 315 | |
dc.identifier.issn | 1535-7163 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/849 | |
dc.identifier.eissn | 1538-8514 | |
dc.identifier.doi | 10.1158/1535-7163.mct-17-0760 | |
dc.description.abstract | Disruption 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.format | Print-Electronic | |
dc.format.extent | 306 - 315 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Cyclin-Dependent Kinases | |
dc.subject | Immunohistochemistry | |
dc.subject | Retrospective Studies | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Biomarkers, Tumor | |
dc.title | Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-10-19 | |
rioxxterms.funder | The Institute of Cancer Research | |
rioxxterms.identifier.project | Unspecified | |
rioxxterms.versionofrecord | 10.1158/1535-7163.mct-17-0760 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cancer therapeutics | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 17 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Target Validation and DNA Damage Response | |
icr.researchteam | Computational Pathology & Integrated Genomics | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Gene Function | |
dc.contributor.icrauthor | Naidoo, Kalnisha | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Campbell, James | |
dc.contributor.icrauthor | Tutt, Andrew | |
dc.contributor.icrauthor | Lord, Christopher | |
dc.contributor.icrauthor | Yuan, Yinyin | |
dc.contributor.icrauthor | Natrajan, Rachael | |