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Title: Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity.
Author: Almendro, Vanessa
Cheng, Yu-Kan
Randles, Amanda
Itzkovitz, Shalev
Marusyk, Andriy
Ametller, Elisabet
Gonzalez-Farre, Xavier
Muñoz, Montserrat
Russnes, Hage G.
Helland, Aslaug
Rye, Inga H.
Borresen-Dale, Anne-Lise
Maruyama, Reo
Oudenaarden, Alexander van
Dowsett, Mitchell
Jones, Robin L.
Reis-Filho, Jorge
Gascón, Pere
Gönen, Mithat
Michor, Franziska
Polyak, Komelia
Keywords: Càncer de mama
Teràpia genètica
Genètica molecular
Breast cancer
Gene therapy
Molecular genetics
Issue Date: 23-Jan-2014
Publisher: Elsevier
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2014, vol. 6, num. 3, p. 514-527
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Medicina)

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