Fig. 4: Timing of the MRCA predicts outcome.
From: Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome
a,b, Event-free (a) and overall survival (b) stratified by mutation density of the MRCA of primary tumors and metastases from the discovery cohort (n = 66; a single tumor lacking survival information was excluded from the analysis). Survival is shown for up to 10 years. P values were computed using the log-rank test; error band represents 95% confidence interval. c, Distribution of mutation densities of the MRCA for the validation cohort. The threshold (0.05 SSNVs per Mb, dashed line) is identical to that of the discovery cohort (compare with Fig. 3a). d,e, Mutation densities of ECA and MRCA for the validation cohort. Top, cumulative SSNV densities of the ECA (dark green) and MRCA (light green) of primary tumors classified as either early-MRCA neuroblastoma (d, n = 22) or late-MRCA neuroblastoma (e, n = 36 with ECA, n = 28 without ECA). e, Left and right panels correspond to tumors with and without timeable ECA, respectively. d,e, Solid lines represent maximum-likelihood estimates and shaded areas represent 95% confidence intervals obtained by nonparametric bootstrapping of chromosomal segments. Bottom, timing of pervasive chromosomal gains; segments compatible with both ECA and MRCA were classified as early, with subclonal gains excluded.
