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Cell Rep DOI:10.1016/j.celrep.2013.12.041

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.

Publication TypeJournal Article
Year of Publication2014
AuthorsAlmendro, V, Cheng, Y-K, Randles, A, Itzkovitz, S, Marusyk, A, Ametller, E, Gonzalez-Farre, X, Muñoz, M, Russnes, HG, Helland, A, Rye, IH, Borresen-Dale, A-L, Maruyama, R, van Oudenaarden, A, Dowsett, M, Jones, RL, Reis-Filho, J, Gascon, P, Gönen, M, Michor, F, Polyak, K
JournalCell Rep
Date Published2014 Feb 13
KeywordsAntineoplastic Agents, Breast Neoplasms, Cell Proliferation, Female, Genetic Heterogeneity, Genetic Variation, Genotype, Humans, Models, Biological, Phenotype

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.


Alternate JournalCell Rep
PubMed ID24462293
PubMed Central IDPMC3928845
Grant ListU54 CA143798 / CA / NCI NIH HHS / United States
U54 CA143874 / CA / NCI NIH HHS / United States
U54CA143798 / CA / NCI NIH HHS / United States
U54CA143874 / CA / NCI NIH HHS / United States