ABSTRACT
According to the models developed, with concurrent oncogenic and/or mutator mutation acquisition and lineage expansion, there will be cell lineages with a subset of the required driver mutations, but not the full complement required for malignant transformation. These lineages may be the cells which constitute premalignant (Table 1) lesions. Moreover, it is likely that a cancer also includes some of these cells, which may have a greater evolutionary fi tness than normal tissue. Particularly if the ecological niche of the tumor is expanding, there is no clear reason these cells should be eliminated. Indeed, in real tumors microheterogeneity is seen with respect to grade and degree of dysplasia.
