The Poisson process is the universal law of cancer development: driver mutations accumulate randomly, silently, at constant rate and for many decades, likely in stem cells

Abstract

BackgroundIt is assumed that cancers develop upon acquiring a particular number of (epi)mutations in driver genes, but the law governing the kinetics of this process is not known. We have recently shown that the age distribution of incidence for 20 most prevalent cancers of old age is best approximated by the Erlang probability distribution. The Erlang distribution describes the probability of several successive random events occurring by the given time according to the Poisson process, which allows to predict the number of critical driver events. ResultsHere we show that the Erlang distribution is the only classical probability distribution that can adequately model the age distribution of incidence for all studied childhood and young adulthood cancers, in addition to cancers of old age. ConclusionsThis validates the Poisson process as the universal law describing cancer development at any age and the Erlang distribution as a useful tool to predict the number of driver events for any cancer type. The Poisson process signifies the fundamentally random timing of driver events and their constant average rate. As waiting times for the occurrence of the required number of driver events are counted in decades, it suggests that driver mutations accumulate silently in the longest-living dividing cells in the body - the stem cells.