Modeling tumor evolutionary dynamics

Abstract

Tumorigenesis can be seen as an evolutionary process, in which the transformation of a normal cell into a tumor cell involves a number of limiting genetic and epigenetic events, occurring in a series of discrete stages. However, not all mutations in a cell are directly involved in cancer development and it is likely that most of them (passenger mutations) do not contribute in any way to tumorigenesis. Moreover, the process of tumor evolution is punctuated by selection of advantageous (driver) mutations and clonal expansions. Regarding these driver mutations, it is uncertain how many limiting events are required and/or sufficient to promote a tumorigenic process or what are the values associated with the adaptive advantage of different driver mutations. In spite of the availability of high-quality cancer data, several assumptions about the mechanistic process of cancer initiation and development remain largely untested, both mathematically and statistically. Here we review the development of recent mathematical/computational models and discuss their impact in the field of tumor biology.

Keywords: modeling; mutation; somatic mutations; tumor; tumorigenesis.

Figure 1

Schematic representation of branching process model of cell division, as proposed by Bozic et al. (2010). According to a specific probabilistic distribution, each cell can either (1) die, (2) divide without acquisition of a new mutation, or (3) divide with acquisition of a new driver mutation.