Inferring tumour proliferative organisation from phylogenetic tree measures in a computational model

We use a computational modelling approach to explore whether it is possible to infer a solid tumour’s cellular proliferative hierarchy under the assumptions of the cancer stem cell hypothesis and neutral evolution. We focus on inferring the symmetric division probability for cancer stem cells, since this is believed to be a key driver of progression and therapeutic response. Motivated by the advent of multi-region sampling and resulting opportunities to infer tumour evolutionary history, we focus on a suite of statistical measures of the phylogenetic trees resulting from the tumour’s evolution in different regions of parameter space and through time. We find strikingly different patterns in these measures for changing symmetric division probability which hinge on the inclusion of spatial constraints. These results give us a starting point to begin stratifying tumours by this biological parameter and also generate a number of actionable clinical and biological hypotheses including changes during therapy, and through tumour evolution.