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

p53 is an important gene, involved in apoptosis (programmed cell death), DNA repair, and cell cycle progression. We explore the selective advantages and disadvantages of mutations in the p53 gene on tumor cells, and the heterogeneity of tumor cell populations. Based on an evolutionary computational approach, our model considers changes in mutation rate caused by lack of DNA repair processes, and the lack of apoptosis caused by mutations in p53. We find that the degree of robustness of p53 to mutations has a significant effect on the tumor heterogeneity and “fitness”, with clinical consequences for people who inherit p53 mutations.