Fig. 1.

Carcinogenesis steps a the standard two-stage clonal expansion (TSCE) model for overall carcinogenesis. Initiation rapid alteration that produces a pre-malignant cell from the pool of normal stem cells; promotion stochastic proliferation of the pre-malignant cells; transformation a second rapid alteration which generates a malignant cell from the pool of pre-malignant cells; progression occurs during the time from the first malignant cell to clinical cancer. b More realistic model of the progression step. After transformation, a lesion may need to progress through bottlenecks, including stochastic extinction and/or dormancy, in order to generate a clinical cancer. If more than one malignant cell is formed by transformation, the different clones evolve independently of each other. For example, the second malignant cell could lead to the first clinical cancer if the first malignant clone becomes extinct, remains dormant indefinitely, or happens to grow slowly