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When, why and how tumour clonal diversity predicts survival

Noble, R. ORCID: 0000-0002-8057-4252, Burley, J. T., Le Sueur, C. & Hochberg, M. E. (2020). When, why and how tumour clonal diversity predicts survival. Evolutionary Applications, 13(7), pp. 1558-1568. doi: 10.1111/eva.13057


The utility of intratumour heterogeneity as a prognostic biomarker is the subject of ongoing clinical investigation. However, the relationship between this marker and its clinical impact is mediated by an evolutionary process that is not well understood. Here, we employ a spatial computational model of tumour evolution to assess when, why and how intratumour heterogeneity can be used to forecast tumour growth rate and progression‐free survival. We identify three conditions that can lead to a positive correlation between clonal diversity and subsequent growth rate: diversity is measured early in tumour development; selective sweeps are rare; and/or tumours vary in the rate at which they acquire driver mutations. Opposite conditions typically lead to negative correlation. In cohorts of tumours with diverse evolutionary parameters, we find that clonal diversity is a reliable predictor of both growth rate and progression‐free survival. We thus offer explanations—grounded in evolutionary theory—for empirical findings in various cancers, including survival analyses reported in the recent TRACERx Renal study of clear‐cell renal cell carcinoma. Our work informs the search for new prognostic biomarkers and contributes to the development of predictive oncology.

Publication Type: Article
Additional Information: © 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher Keywords: cancer, computational model, evolutionary dynamics, evolutionary forecasting, prognostic biomarkers
Subjects: Q Science > QA Mathematics
Q Science > QD Chemistry
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Departments: School of Science & Technology > Mathematics
SWORD Depositor:
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