Feb 11, 2014

Evolution of intratumoral phenotypic heterogeneity: the role of trait inheritance

Interface Focus
Jill A Gallaher, Alexander R A Anderson


A tumour is a heterogeneous population of cells that competes for limited resources. In the clinic, we typically probe the tumour by biopsy, and then characterize it by the dominant genetic clone. But genotypes are only the first link in the chain of hierarchical events that leads to a specific cell phenotype. The relationship between genotype and phenotype is not simple, and the so-called genotype to phenotype map is poorly understood. Many genotypes can produce the same phenotype, so genetic heterogeneity may not translate directly to phenotypic heterogeneity. We therefore choose to focus on the functional endpoint, the phenotype as defined by a collection of cellular traits (e.g. proliferative and migratory ability). Here, we will examine how phenotypic heterogeneity evolves in space and time and how the way in which phenotypes are inherited will drive this evolution. A tumour can be thought of as an ecosystem, which critically means that we cannot just consider it as a collection of mutated cells but more as a complex system of many interacting cellular and microenvironmental elements. At its simplest, a growing tumour with increased proliferation capacity must compete for space as a limited resource. Hypercellularity leads...Continue Reading

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Mentioned in this Paper

Tumor Lysis Syndrome
Genetic Inheritance
Genotype Determination
Biopsy Procedures on the Pharynx, Adenoids, and Tonsils
Phenotype Determination
Cell Phenotype Determination Procedure

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