Figure 4.

Clinical and genomic features associated with ecDNA. A, Oncoprint illustrating clinical and genomic attributes between the 488 tumors categorized into three groups based on fSCNA status: without fSCNA (n = 210 patients), without non–ecDNA-based amplifications (other fSCNA, n = 93 patients), and with ecDNA amplification (n = 185 patients). Each column represents a patient, ordered by the number of SVs from highest to lowest. For patients with multiregional WGS data, we calculated the average value of each parameter across all tumors for statistical analysis. AMP, amplification; BFB, breakage–fusion–bridge; FGA, the fraction of genome altered; TMB, tumor mutation burden; WGD, whole genome duplication. B, Kaplan–Meier plot depicting the overall survival of 488 patients with urothelial carcinoma stratified by fSCNA status. The P value was calculated using a log-rank test. C, Forest plot showing the results of a multivariate Cox proportional hazards model adjusting for tumor stage. The error bars represent the 95% CIs of the HRs. D, Forest plot depicting the associations between the presence or absence of ecDNA and various genomic characteristics, such as the number of SVs, ploidy status, FGA, WGD events, chromothripsis, TMB, neoantigen load, and the frequency of OncoKB level 1 mutation. The analysis was adjusted for the tumor stage. Error bars represent 95% CIs for the OR estimates. OncoKB level 1 mutation: “FDA-recognized” biomarker predictive of response to an “FDA-approved drug” in this indication. E, Forest plot illustrating the results of a regression model that examines the association between the presence of ecDNA or non-ecDNA amplifications and the odds of harboring high-impact driver gene mutations in tumors from the entire urothelial carcinoma cohort (n = 488 patients). The analysis was adjusted for the tumor stage. Error bars represent 95% CIs for the OR estimates. F, Fraction of tumors with MDM2-containing ecDNA (MDM2-ecDNA⁺), ecDNA⁺MDM2/4⁻ (ecDNA without MDM2/4 amp.), ecDNA⁻MDM2/4⁺ (MDM2/4 amp. without ecDNA), and ecDNA⁺MDM2/4+ (MDM2/4 amp. with ecDNA), grouped by TP53 mutation status. The P value was calculated using a χ² test. MUT, mutated; WT, wild-type.