Modeling the effect of p53 on tumor heterogeneity and the mutator phenotype

Abstract

p53 is an important gene, involved in apoptosis (programmed celldeath), DNA repair, and cell cycle progression. We explore theselective advantages and disadvantages of mutations in the p53 geneon tumor cells, and the heterogeneity of tumor cell populations.Based on an evolutionary computational approach, our model considerschanges in mutation rate caused by lack of DNA repair processes, andthe lack of apoptosis caused by mutations in p53. We find that thedegree of robustness of p53 to mutations has a significant effect onthe tumor heterogeneity and "fitness", with clinical consequencesfor people who inherit p53 mutations.