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J Theor Biol. 2006 Jun 21;240(4):521-30. Epub 2005 Dec 15.

Stochastic dynamics of metastasis formation.

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Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA.


Tumor metastasis accounts for the majority of deaths in cancer patients. The metastatic behavior of cancer cells is promoted by mutations in many genes, including activation of oncogenes such as RAS and MYC. Here, we develop a mathematical framework to analyse the dynamics of mutations enabling cells to metastasize. We consider situations in which one mutation is necessary to confer metastatic ability to the cell. We study different population sizes of the main tumor and different somatic fitness values of metastatic cells. We compare mutations that are positively selected in the main tumor with those that are neutral or negatively selected, but faster at forming metastases. We study whether metastatic potential is the property of all (or the majority of) cells in the main tumor or only the property of a small subset. Our theory shows how to calculate the expected number of metastases that are formed by a tumor.

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