Fig. 5
CDKAL1P409L mutation decreased the sensitivity of cancer cells to docetaxel treatment. A Somatic and germline mutations in the 47 pre-treatment tumors and matched germline DNA. Samples were annotated for clinicopathological and molecular features (top panel). The types of somatic (middle panel) and germline (bottom panel) mutations of the indicated genes for each sample are displayed with colored squares. The histograms on the right-hand side show the accumulated number of alterations among the SMGs identified by the MuSiC2 (FDR < 0.1) or the pathogenic germline mutations classified in the ClinVar database. AJCC, The American Joint Committee on Cancer. B The distribution of potentially deleterious mutations in CDKAL1 and CENPT in the nonresponsive and responsive pre-treatment groups (left). Diagrams representing the protein domains of potentially deleterious mutations (right). The “lollipopPlots” were generated using the maftools R package and manually edited. C The CDKAL1 expression in different human breast cancer cell lines as indicated was examined by western blot. D The expression of CDKAL1WT and CDKAL1P409L in HCC1806 and MDA-MB-231 cells infected with empty vector, CDKAL1WT and CDKAL1P409L lentiviruses by western blot and quantitative real-time PCR (qPCR) analyses. E IC50 assays of docetaxel. The proliferation of HCC1806 and MDA-MB-231 cells as described in (D) were determined with a CCK-8 cell counting kit at an increasing dose of docetaxel as indicated. The significance of relative IC50 values between CDKAL1WT and CDKAL1P409L cells with that of CDKAL1WT cells as 1.0 were analyzed by paired t-test. Data represent mean ± SD (n = 3). *, P < 0.05; **, P < 0.01