The dynamics of gene amplification described as a multitype compartmental model and as a branching process

DOI10.1016/0025-5564(91)90094-YMaRDI QIDQ2277181zbMATH OpenOpenAlexWikidataFDO

Authors L. E. Harnevo, Zvia Agur

Publication date 1991

Published in Mathematical Biosciences (Search for Journal in Brave)

Full work available at URL https://doi.org/10.1016/0025-5564(91)90094-y

zbMATH Keywords

a.s. extinctiondifference equationsdrug resistancedrug sensitive cellsdynamics of gene amplificationexpectation matrixGalton-Watson processmultitype branching processprobability generating functiontreatment of cancer

Mathematics Subject Classification ID

Applications of branching processes (60J85) Biochemistry, molecular biology (92C40)

Review text

Gene amplification (GA) is by now a well-documented phenomenon in many natural areas and it can be regarded as one of the mechanisms that yield to drug resistance in the treatment of cancer. In this paper various mathematical models are developed to describe the dynamics of gene amplification. At first, using difference equations, some expressions are given for the expectations of certain random variables such as the number of cells having k copies of a specified gene or the size of drug sensitive cells with the loss of cells taken either as constant or as copy-number dependent. It is found that for one-copy GA processes the relative frequency of sensitive cells converges to zero in the case of a constant loss probability and otherwise it has a lower bound. In the second part the GA for single-gene-copy cells is described by a branching process which leads to formulas for the probability generating function (PGF) and the expectation, which are similar to those presented in the first part, and for the variance. A simple consequence then leads to conditions for a.s. extinction. Afterwards for a simple three-type model the PGF and the expectation matrix are given. Finally, the gene amplification is described as a general multitype branching process where the expectation matrix is given for different GA situations such as stable or unstable one-copy and multi-copy GA.

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