Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution
Fig 2
Frequency of passenger mutations.
(A-B) Cumulative distribution function for the first three successful mutations. The y-axis shows the probability that the mutation has a frequency of less than α. Comparison between formula (2) and exact computer simulations of the stochastic process with death-birth ratios δ = 0.72 (A) and δ = 0.99 (B). For δ = 0.72, the median frequencies of the first three successful mutations are below 5%. For δ = 0.99, they are all above 40%. (C-D) Mutation frequency versus time of appearance. (C) Mean frequency attained by a mutation which arose when there were z other cells in the population, for different values of the death-birth ratio, δ. (D) Maximum likelihood and maximum a posteriori estimate (which are approximately equal) for the number of cells in the population when the mutation with frequency α arose. Passenger mutation rate u = 0.015 (product of the number of basepairs in the exome, L ∼ 3 ⋅ 107, and the normal point mutation rate during cell division, μ ∼ 5 ⋅ 10−10).