Dynamics of metastasis suppressor gene inactivation.
For most cancer cell types, the acquisition of metastatic ability leads to clinically incurable disease. Twelve metastasis suppressor genes (MSGs) have been identified that reduce the metastatic propensity of cancer cells. If these genes are inactivated in both alleles, metastatic ability is promoted. Here, we develop a mathematical model of the dynamics of MSG inactivation and calculate the expected number of metastases formed by a tumor. We analyse the effects of increased mutation rates and different fitness values of cells with one or two inactivated alleles on the ability of a tumor to form metastases. We find that mutations that are negatively selected in the main tumor are unlikely to be responsible for the majority of metastases produced by a tumor. Most metastases-causing mutations will be present in all (or most) cells in the main tumor.
Michor
Franziska
F
Harvard Society of Fellows, Harvard Program for Evolutionary Dynamics, Cambridge, MA 02138, USA. michor@fas.harvard.edu
Iwasa
Yoh
Y
D000818:Animals; D003198:Computer Simulation; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D008957:Models, Genetic; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics*; D013269:Stochastic Processes