15357163mct170760-sup-187545_2_supp_4339701_vy1vn9.xlsx (146.91 kB)

Supplementary Tables S1-S10 from Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response–Targeted Therapies in Breast Cancer

dataset

posted on 2023-04-03, 16:11 authored by Kalnisha Naidoo, Patty T. Wai, Sarah L. Maguire, Frances Daley, Syed Haider, Divya Kriplani, James Campbell, Hasan Mirza, Anita Grigoriadis, Andrew Tutt, Paul M. Moseley, Tarek M.A. Abdel-Fatah, Stephen Y.T. Chan, Srinivasan Madhusudan, Emad A. Rhaka, Ian O. Ellis, Christopher J. Lord, Yinyin Yuan, Andrew R. Green, Rachael Natrajan

Supplementary Table S1: CDK12 expression in relation to clinicopathological parameters for the unselected TMA series; Supplementary Table S2: CDK12 expression in relation to clinicopathological parameters for the HER2-positive Herceptin treated series; Supplementary Table S3: CDK12 expression in relation to clinicopathological parameters for the METABRIC TMA series; Supplementary Table S4: Univariate and multivariate analysis of CDK12 in the TMA cohorts; Supplementary Table S5: CDK12 mutations in breast cancer. Taken from cBioportal (42,43); Supplementary Table S6: Correlations of CDK12 mutations, methylation, gene expression and ERBB2 copy number in primary breast cancers from TCGA; Supplementary Table S7: Correlations of CDK12 mutations and gene expression of DNA repair genes in primary tumors from METABRIC. P values from heteroscedastic 2-tailed, t-test; Supplementary Table S8: Correlations of CDK12 protein expression, and miRNA expression in primary tumors from METABRIC. Wilcoxon rank P values are corrected for multiple testing; Supplementary Table S9: Correlations of CDK12 protein expression and gene expression of DNA repair genes in primary tumors from METABRIC. Limma analysis corrected for multiple testing; Supplementary Table S10: Association of CDK12 absent and intermediate (0, 2-6) versus high (7-8) expression with DNA repair proteins in unselected and TNBC. P values from Fishers exact test.

Funding

Breast Cancer Research Foundation

History

ARTICLE 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.