Epigenetic carcinogenesis and genetic instability: competitive aspects of the malignant phenotype.

Abstract

The proposal that carcinogenesis results from the somatic inheritance of defective epigenetic transmission is consistent with the establishment of genetic instability and the generation of a clonally divergent population of cells expressing anomalous structural and functional characteristics. The majority of these uncoordinated properties would be expected to be deleterious, thus placing cancer cells at a proliferative disadvantage. To compensate for this the malignant phenotype requires a property that enables the deviant cells to survive proliferative competition. This question is explored using a competitive growth model based on viewing cell populations as existing in microenvironmental domains subject to a barrier to migration. The model demonstrates that the ability to penetrate this migratory barrier is sufficient to permit otherwise less competitive cells to proliferate and expand the anomalous population. The possible nature of the domain barrier is briefly discussed.