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Published on: September 29, 2011
Modelling the evolution of genetic instability during tumour progression
Ruchira S Datta1, Alice Gutteridge, Charles Swanton
1Center for Evolution and Cancer, University of California San Francisco San Francisco, CA, USA.
Evolutionary Applications
|February 12, 2013
Summary
Genetic instability evolves in tumors when cancer-driving mutations offer moderate fitness benefits. This study clarifies how selection shapes mutation patterns during cancer development.
Area of Science:
- Evolutionary biology
- Cancer research
- Genetics
Background:
- The role of genetic instability in carcinogenesis is debated.
- Genetic instability may accelerate or retard tumor growth.
- It is unclear if genetically unstable clones are more advantageous.
Purpose of the Study:
- To determine the circumstances under which genetic instability evolves during tumor progression.
- To model the evolution of tumor subclones and mutator phenotypes.
Main Methods:
- Utilized a Wright-Fisher type model to simulate tumor subclone evolution.
- Incorporated advantageous, deleterious, and mutator mutations.
- Analyzed the impact of selection strength on the evolution of genetic instability.
Main Results:
- Cancers evolve a mutator phenotype when driver mutations provide moderate fitness advantages.
- Strong or weak selection for driver mutations suppresses the evolution of mutator phenotypes.
- Genetic instability arises secondary to advantageous driver mutations.
Conclusions:
- Selection plays a critical role in shaping mutation patterns during carcinogenesis.
- The evolution of genetic instability is contingent on the strength of selection for driver mutations.
- Deleterious mutations have a limited impact on genetic instability evolution unless selection is weak or deleterious mutations are frequent.
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