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Space (arbitrary units)

Fig. 9.8 Tumor progression if the initial mutant cell line has shifted the balance between promoters and inhibitors more substantially towards promotion. Now, multiple foci can develop without the need for further mutations. The multiple foci develop, however, by first generating a single lesion which subsequently splits to give rise to two lesions during the natural growth process. Parameters were chosen as follows: r = 1;<5 = 0.1; ap = 5; bp = 0.1; a/ = 1; 6/ = 0.01; Dc = 0.00001; Dj = 0.001, L = 2.

the lower the chance that the relative population size of the mutants can cross this threshold. If this cannot occur, further cancer progression not only requires the generation of a mutation which enhances the level of promotion, but an additional mutation which gives the promoter mutant a selective advantage over the rest of the cell population. That is, in addition to the mutation which shifts the balance in favor of promotion, a mutation is required either in an oncogene or a tumor suppressor gene so that the mutant can grow to sufficiently high numbers or fixation.

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