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Estimation of Spontaneous Mutation Rates

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Abstract:

Summary. 

Spontaneous or randomly occurring mutations play a key role in cancer progression. Estimation of the mutation rate of cancer cells can provide useful information about the disease. To ascertain these mutation rates, we need mathematical models that describe the distribution of mutant cells. In this investigation, we develop a discrete time stochastic model for a mutational birth process. We assume that mutations occur concurrently with mitosis so that when a nonmutant parent cell splits into two progeny, one of these daughter cells could carry a mutation. We propose an estimator for the mutation rate and investigate its statistical properties via theory and simulations. A salient feature of this estimator is the ease with which it can be computed. The methods developed herein are applied to a human colorectal cancer cell line and compared to existing continuous time models.

Keywords: Cancer; Luria-Delbrück distribution; Mutation rate; Stochastic processes

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/1541-0420.00065

Affiliations: 1: Department of Family and Preventive Medicine, University of California-, La Jolla, California 92093, U.S.A. 2: Klinik Innere Medizin 4, Wahringer Gurtel 18, A-1090 Vienna, Austria

Publication date: September 1, 2003

bpl/biom/2003/00000059/00000003/art00010
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