波江野　洋（九大・理・生物）
(Kyushu University)

10月23日（火）　１３：３０〜　 (理学部3号館6階数理生物学セミナー室)

Knudson's two-hit hypothesis proposes that two genetic changes in the RB1 gene are the rate-limiting steps of retinoblastoma. In the inherited form of this childhood eye cancer, only one mutation emerges during somatic cell divisions while in sporadic cases, both alleles of RB1 are inactivated in the growing retina. Sporadic retinoblastoma serves as an example of a situation in which two mutations are accumulated during clonal expansion of a cell population. Other examples include evolution of resistance against anti-cancer combination therapy and inactivation of both alleles of a metastasis suppressor gene during tumor growth. In this talk, we consider an exponentially growing population of cells that must evolve two mutations to evade treatment or to display a disease phenotype. We calculate the probability that the population has evolved both mutations before it reaches a certain size. This probability depends on the rates at which the two mutations arise, the growth and death rates of cells carrying none, one or both mutations, and the size the cell population reaches. Further, we develop a formula for the expected number of cells carrying both mutations when the final population size is reached. Our theory establishes an understanding of the dynamics of two mutations during clonal expansion.

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