Figure 3. Maintenance of fit somatic stem cells limits tumor development.

A. When mutations and epigenetic changes (heritable damage) accumulate to the point where the buffering capacity of the stem cell pool is exhausted (denoted by vertical dotted line), the fitness of the stem cell population will begin to decline. Declining fitness will then increase selective pressure for adaptive oncogenic mutations that in turn promote cancer initiation. B. Proposed model for how vertebrates with large differences in somatic cell numbers (10³–10⁷ fold) and lifespans (10–100 fold) similarly avoid cancer through reproductive years.