Mathematical Biology seminar Doug Grossman Huntsman Cancer Institute, University of Utah ""Multi-step skin carcinogenesis" December 8 3:05pm in LCB 215 The mechanism by which a single mutant cell clonally expands is usually assumed to involve an additional mutation in a cell cycle regulatory gene. An alternative mechanism for driving clonal expansion is apoptosis, which might create vacant stem cell compartments that can be re-populated by mutant cells. This model predicts that in a mouse with reduced apoptosis capacity i) more mutated cells will appear initially but ii) these cells will expand into clones more slowly than in wild-type animals. Experiments with transgenic mice with reduced apoptosis show that apoptosis does appear to suppress two stages that involve new mutations - initiation and malignant conversion - yet drives clonal expansion of existing mutant cells.