Figure 4. Reconstruction of the mutational timeline in each patient.
The allelic frequency of a mutation within the tumor predicts the size of the tumor when the mutation occurred. (A,B) The deconvolution of the mutational timeline is illustrated for samples TB and TCGA-AA-3712 respectively. Whereas established CRC drivers (APC, KRAS, TP53) were found to be present from the first malignant cell, several recurrent putative drivers not yet validated were mutated after malignant seeding, despite the underlying neutral dynamics. This suggests that some of these candidate alterations may not be fundamental drivers of growth in all cases. Confidence intervals are calculated using a binomial test on the number of variant reads versus the depth of coverage for each mutation.