Fig. 4

Timing of driver mutations using single and multiple tumor samples. Driver mutations were annotated as those found in driver genes identified in the previous report [12]. a Fraction of driver mutations occurring at early time. For the single sample data set (left), we generated 100 replicates, where we randomly selected a single sector per patient. For each replicate, we pooled driver mutations and computed the fraction of early driver mutations (mean: 66%). For multiple samples (right), all samples available for each data set were used to compute the fraction of early driver mutations (45%). The fraction of early drivers found in 100 replicates of single-tumor sampling was statistically greater than the early driver fraction found using multiple samples by single single-sample t test (P < 10⁻¹⁵). b Difference between late-and early-driver mutation fraction calculated using single-tumor samples (one replicate is shown). Each bar represents a patient: pink marks patients that have a greater fraction of early-driver mutations than late, and blue marks patients that show an opposite trend. Eleven patients contained equal proportions of early and late drivers, and 7 patients were removed as no driver mutations were identified