High-Complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance

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Abstract

It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400 000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analyzed. Fractionated IR induced a strong selective pressure for clonal reduction which significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to-clone difference within tumor cell lines. IR induced clonal reduction affected the majority of tumor cells ranging between 96% and 75% and correlated to the degree of radiation sensitivity. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. A 2-fold increase in radiation resistance results in a 4-fold (P

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Wursthorn, A., Schwager, C., Kurth, I., Peitzsch, C., Herold-Mende, C., Debus, J., … Nowrouzi, A. (2022). High-Complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance. International Journal of Cancer, 150(4), 663–677. https://doi.org/10.1002/ijc.33855

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