Oncogenic mutational/epigenetic events: Deterministic, stochastic or random: Implications for hypoxic cancer cells and tumor heterogeneity

Abstract

Many cancers have been characterized by their expression of multiple "driver" oncogenes [1]. This implies a sequence of crucial developmental "decisions" required to implement an oncogenic "program". Are all or at least most of these decisions deterministic and others "stochastic" in implementation? Certain inborn errors of metabolism and hereditary cancers are largely deterministic. And yet to account for the widespread differences in detail of gene expression within and between cancer cells from different regions of the same cancer, to what extent are these variations at a fine-grained level subject to "decision trees" or "nodes" that may often depend upon stochastic events, engrafted on to more fundamental cell, tissue, organ or unfolding aberrant cancer-oriented deterministic programs [2,3]? Considering that many epithelial cancers develop over a number of years, does an admixture of determinative and stochastic decision-events contribute to a protracted maturation of epithelial cancers? The potential effect of cellular stress such as that due to hypoxia on the outcomes from stochastic events is uncertain.We consider some of these questions, employing a differential-logistic Monte Carlo simulation with continued stochastic input to a fixed carrying capacity, K, of slowly and rapidly proliferating daughter cancer cells as a visual model for this discussion. An Appendix with further details of the programs employed is provided at: www.uic.edu/nursing/publicationsupplements/stochastic Anderson Rubenrstein Guinan Patel.pdf