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Data from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer
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Data from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer
Data from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer
KN
Kalnisha Naidoo
Kalnisha Naidoo
PW
Patty T. Wai
Patty T. Wai
SM
Sarah L. Maguire
Sarah L. Maguire
FD
Frances Daley
Frances Daley
SH
Syed Haider
Syed Haider
DK
Divya Kriplani
Divya Kriplani
JC
James Campbell
James Campbell
HM
Hasan Mirza
Hasan Mirza
AG
Anita Grigoriadis
Anita Grigoriadis
AT
Andrew Tutt
Andrew Tutt
PM
Paul M. Moseley
Paul M. Moseley
TA
Tarek M.A. Abdel-Fatah
Tarek M.A. Abdel-Fatah
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3 April 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1535-7163.c.6539677.v1
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.
Keywords
CDK12 PROTEIN
SALTS
DEFECTS
BREAST CANCER
FUNCTION
SURVIVAL
DDR
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Open Access