Extended Data Fig. 3: Mediation links ecDNA to known prognostic markers.
From: Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma
Log-normal accelerated failure time (AFT) regression models estimating relative time to progression or death of n = 340 patients. (a) Model diagram of proposed mediation by ecDNA of the effect of TP53 mutation on survival. According to this model, TP53 inactivation generates genome instability, facilitating the formation of ecDNA, which then affects survival. (b) Forest plot of μ coefficients (log time ratios) of AFT model including age, sex, subgroup and TP53 mutation status as covariates. The estimate μp53_mut = −1.5 indicates 1-exp(μp53_mut) = 77% reduction in expected survival time for medulloblastoma patients with TP53-mutant tumors. (c) μ coefficients of AFT model including ecDNA as an additional covariate estimates 56% reduction in survival time for patients with ecDNA-positive (ecDNA+) tumors and an insignificant and reduced coefficient TP53 for mutation, indicating partial mediation by ecDNA of the effect of TP53 mutation on survival. Data in (b) and (c) are presented as maximum likelihood estimate (MLE) +/− 95% confidence intervals.
