Population genetics of tumor suppressor genes

Cancer emerges when a single cell receives multiple mutations. For example, the inactivation of both alleles of a tumor suppressor gene (TSG) call imply a net reproductive advantage of the cell and might lead to clonal expansion. In this paper. we calculate the probability as a function of time that a population of cells has generated at least one cell with two inactivated alleles of a TSG. Different kinetic laws hold for small and large populations. The inactivation of the first allele can either be neutral or lead to a selective advantage or disadvantage. The inactivation of the first and of the second allele can occur at equal or different rates. Our calculations provide insights into basic aspects Of Population genetics determining cancer initiation and progression. (C) 2004 Elsevier Ltd. All rights reserved.