Ergodicity Breaking and Self-Destruction of Cancer Cells by Induced Genome Chaos

Abstract

During the progression of some cancer cells, the degree of genome instability may increase, leading to genome chaos in populations of malignant cells. While normally chaos is associated with ergodicity, i.e., the state when the time averages of relevant parameters are equal to their phase space averages, the situation with cancer propagation is more complex. Chromothripsis, a catastrophic massive genomic rearrangement, is observed in many types of cancer, leading to increased mutation rates. We present an entropic model of genome chaos and ergodicity and experimental evidence that increasing the degree of chaos beyond the non-ergodic threshold may lead to the self-destruction of some tumor cells. We study time and population averages of chromothripsis frequency in cloned rhabdomyosarcomas from rat stem cells. Clones with frequency above 10% result in cell apoptosis, possibly due to mutations in the BCL2 gene. Potentially, this can be used for suppressing cancer cells by shifting them into a non-ergodic proliferation regime.