Fig. 1. Mutational analysis of selected genes.

a Heatmap of selected genes based on whole exome sequencing. Kaplan–Meier plots stratified by mutation vs mutation not detected in the overall cohort for b PBRM1; c BAP; and d SETD2. e Forest plot for treatment arm effect of gene mutations and DFS association stratified by mutation vs mutation not detected. Data are presented as hazard ratio (HR) and 95% CI. Kaplan–Meier plots stratified by mutation vs mutation not detected in the overall cohort for f MTOR; and g ARID1A. h Heatmap of gene mutations that influenced sunitinib treatment outcome based on whole exome sequencing. i Forest plot for treatment arm effect of additional gene mutations and DFS association stratified by mutation vs mutation not detected. Data are presented as HR and 95% CI. HR <1 indicates longer DFS in mutation group; HR >1 indicates longer DFS in mutation not detected group. ¹Cox proportional hazards model with <median as the reference group was used to calculate HR and 95% CI. ²Cox regression HR p-value is used to compare between Wild Type/Mutation groups. A HR <1 indicates better survival in the Mutation group, while a HR >1 indicates better survival in the Wild Type group. HR reference level is <median, p-value is from Logrank test. ³Two-sided p-value for overall Wild Type/Mutation-by-treatment interaction from Cox model with treatment group and wild-type/mutation status as two independent variables. ARID1A AT-rich interaction domain 1A, BAP1 BRCA1-associated protein 1, CI confidence interval, CSPG4 chondroitin sulfate proteoglycan 4, CTCFL CCCTC-binding factor-like, DFS disease-free survival, ERICH6B glutamate-rich 6B, HR hazard ratio, KMT2 lysine methyltransferase 2D, MTOR mechanistic target of rapamycin kinase, NE not estimable, PBR1 proline-rich protein BstNI subfamily 1, PPIP5K1 diphosphoinositol pentakisphosphate kinase, SETD2 SET domain-containing 2, histone lysine methyltransferase, THEMIS thymocyte selection-associated, TMB tumor mutational burden, TP53 tumor protein 53, VHL Von Hippel-Lindau tumor suppressor, WDFY4 WDFY family member 4.