Figure 1

Step-wise accumulation of specific gene defects. Mutations (red triangles) trigger the built-in cell killer function (red asterisks). m(0), normal cells; m(1), m(2), m(3), m(n), mutant cells with 1, 2, 3, and n defects in cancer-related genes, respectively. (a), (b), (c), (n), selection "sieves" which determine the stages of transformation. The trigger "count-down" is shown on the left. Double-headed arrows indicate that transformation and trigger steps are amenable to species- and tissue-specific variations (see text).