Fig. 7. PRKDC non-silent somatic mutations are associated with poor clinical outcomes.
a Lollipop plot for PRKDC mutations identified in a set of 640 tamoxifen-treated, clinically ER + patients. Green-filled circles denote missense mutation and black-filled circles denote truncating mutations. Protein domains are indicated as follows: green, NUC194 domain B in the catalytic subunit of DNA-dependent protein kinases; red, FAT domain present in the PIK-related kinases; dark-blue, Phosphoinositide 3-kinase (PI3K) domain. A complete description of PRKDC mutations has been previously published and can be found in Supplementary data 3 of Griffith et al.42. Mutation pathogenicity, clinical annotation of death due to disease, and DNA-PKcs expression categories by IHC for the corresponding cases are displayed. b Boxplots showing the expression levels of DNA-PKcs by IHC according to mutation status and its type. The median (center bar), and the third and first quartiles (upper and lower edges, respectively) are shown. c Kaplan–Meier curve for BCSS in the subgroup of ER + cases treated with tamoxifen in the BC Cancer series according to PRKDC mutation status (n = 409). d Kaplan–Meier curves for OS in the TCGA cohort of invasive breast cancer according to PRKDC mutation status (n = 818). Abbreviations: ER estrogen receptor, BCSS breast cancer-specific survival, OS overall survival, IHC immunohistochemistry.