@article {129,
	title = {Stochastic modelling of tumorigenesis in p53 deficient mice.},
	journal = {Br J Cancer},
	volume = {77},
	year = {1998},
	month = {1998},
	pages = {243-52},
	abstract = {<p>Stochastic models of tumorigenesis have been developed to investigate the implications of experimental data on tumour induction in wild-type and p53-deficient mice for tumorigenesis mechanisms. Conventional multistage models in which inactivation of each p53 allele represents a distinct stage predict excessively large numbers of tumours in p53-deficient genotypes, allowing this category of model to be rejected. Multistage multipath models, in which a p53-mediated pathway co-exists with one or more p53-independent pathways, are consistent with the data, although these models require unknown pathways and do not enable age-specific curves of tumour appearance to be computed. An alternative model that fits the data is the {\textquoteright}multigate{\textquoteright} model in which tumorigenesis results from a small number of gate-pass (enabling) events independently of p53 status. The role of p53 inactivation is as a rate modifier that accelerates the gate-pass events. This model implies that wild-type p53 acts as a {\textquoteright}caretaker{\textquoteright} to maintain genetic uniformity in cell populations, and that p53 inactivation increases the probability of occurrence of a viable cellular mutant by a factor of about ten. The multigate model predicts a relationship between the time pattern of tumour occurrence and tumour genotype that should be experimentally testable. Stochastic modelling may help to distinguish {\textquoteright}gatekeeper{\textquoteright} and {\textquoteright}caretaker{\textquoteright} genes in other tumorigenic pathays.</p>},
	keywords = {Animals, Gene Deletion, Genes, p53, Mathematics, Mice, Mice, Knockout, Models, Biological, Mutation, Neoplasms, Experimental, Neoplastic Stem Cells, Stochastic Processes},
	issn = {0007-0920},
	author = {Jiang-Hua Mao and Lindsay, K A and Balmain, A and Wheldon, T E}
}
