City Research Online

Abstract

Characterizing the mode – the way, manner, or pattern – of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. Sequencing studies have inferred various modes, including branching, punctuated, and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour. Here we propose that tumour architecture is key to explaining the variety of observed genetic patterns. We examine this hypothesis using spatially explicit population genetic models and demonstrate that, within biologically relevant parameter ranges, di↵erent spatial structures can generate four tumour evolutionary modes: rapid clonal expansion; progressive diversification; branching evolution; and effectively almost neutral evolution. Quantitative indices are presented for describing and classifying these evolutionary modes. Using these indices, we show that our model predictions are consistent with empirical observa26 tions for cancer types with corresponding spatial structures. The manner of cell dispersal and the range of cell-cell interaction are found to be essential factors in accurately characterizing, forecasting and controlling tumour evolution.

Publication Type:	Article
Subjects:	Q Science > QM Human anatomy R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Departments:	School of Science & Technology > Mathematics
SWORD Depositor:	Symplectic Administrator

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