Mutator mutations enhance tumorigenic efficiency across fitness landscapes.

ABSTRACT:

Background

Tumorigenesis requires multiple genetic changes. Mutator mutations are mutations that increase genomic instability, and according to the mutator hypothesis, accelerate tumorigenesis by facilitating oncogenic mutations. Alternatively, repeated lineage selection and expansion without increased mutation frequency may explain observed cancer incidence. Mutator lineages also risk increased deleterious mutations, leading to extinction, thus providing another counterargument to the mutator hypothesis. Both selection and extinction involve changes in lineage fitness, which may be represented as "trajectories" through a "fitness landscape" defined by genetics and environment.

Methodology/principal findings

Here I systematically analyze the relative efficiency of tumorigene

SUBMITTER: Beckman RA 

PROVIDER: S-EPMC2690659 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature