Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/101862
Title: | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity. |
Author: | Almendro Navarro, Vanessa Cheng, Yu-Kan Randles, Amanda Itzkovitz, Shalev Marusyk, Andriy Ametller, Elisabet Gonzalez-Farre, Xavier Muñoz Mateu, Montserrat Russnes, Hage G. Helland, Åslaug 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, Kornelia |
Keywords: | Càncer de mama Teràpia genètica Fenotip Genètica molecular Estadística Breast cancer Gene therapy Phenotype Molecular genetics Statistics |
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: http://dx.doi.org/10.1016/j.celrep.2013.12.041 |
It is part of: | Cell Reports, 2014, vol. 6, num. 3, p. 514-527 |
URI: | http://hdl.handle.net/2445/101862 |
Related resource: | http://dx.doi.org/10.1016/j.celrep.2013.12.041 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
662561.pdf | 5.94 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License