On measuring selection in cancer from subclonal mutation frequencies
Fig 2
Cancer cell frequency of a subclonal driver is biased towards 0 and 1.
a, b, c, Probability that a subclonal driver is in the detectable range (0.2 ≤ fsub ≤ 0.8), and thus able to skew the distribution of mutational cancer cell frequencies expected from neutral evolution, for three parameter regimes. For each parameter regime, we depict three levels of selection: moderate selection (driver increases net growth rate by g = 30%), strong selection (g = 70%), and very strong selection (g = 100%). Parameter values for a, moderately growing tumor [20]: b = 0.14, r = 0.01; b, fast growing tumor [36]: b = 0.25, r = 0.07; c, slow-growing tumor [21]: b = 0.33, r = 0.0013. Driver mutation rate [21] u = 10−5. All rates are per day and b = b1. d, e, f, Probability density for the frequency of a subclonal driver that increases the net growth rate by 70%, in a moderately growing tumor (a). d, Driver frequency is biased towards 0 when tumor size is small. e, When tumor size is large, driver frequency is biased towards 1. f, When detection is most likely (at intermediate size), driver frequency distribution is almost flat.