Evolutionary maintenance of oncogenesis.

Background: Transformation of normal cells into cells with malignant phenotypes is often the result of loss of tumor suppressor gene (TSG) function after exposure to a carcinogen.

Conclusions: We propose that TSGs susceptible to mutation and consequent loss of function are evolutionarily preserved in normal cell genomes so that the cells survive mutation-inducing insults and thereby evade apoptosis. While the mutations produced in TSGs confer cellular persistence and preclude apoptosis, oncogenesis is the untoward consequence. Proto-oncogenes might similarly be maintained and contain evolutionarily selected and fixed sequences susceptible to mutations (oncogene activation) that prevent cell death but ironically result in host death from malignancy.