@article{33e3db244e0a4ddeb75aa8b37e350e18,
title = "Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity",
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.",
author = "Vanessa Almendro and Cheng, {Yu Kang} and Amanda Randles and Shalev Itzkovitz and Andriy Marusyk and Elisabet Ametller and Xavier Gonzalez-Farre and Montse Mu{\~n}oz and Russnes, {Hege G.} and {\AA}slaug Helland and Rye, {Inga H.} and Borresen-Dale, {Anne Lise} and Reo Maruyama and Alexander vanOudenaarden and Mitchell Dowsett and Jones, {Robin L.} and Jorge Reis-Filho and Pere Gascon and Mithat G{\"o}nen and Franziska Michor and Kornelia Polyak",
note = "National Cancer Institute Physical Sciences Oncology Center [U54CA143874, U54CA143798]; Susan G. Komen Foundation; Cellex Foundation; Redes Tematicas de Investigacion en Cancer [RD12/0036/0055]; Breast Cancer Research Foundation; U.S. Department of Energy by Lawrence Livermore National Laboratory [DE-AC52-07NA27344]We thank members of our laboratories for their critical reading of this manuscript and useful discussions. We thank Lisa Cameron in the DFCI Confocal Microscopy for her technical support. This work was supported by the National Cancer Institute Physical Sciences Oncology Center U54CA143874 (to A.v.O.) and U54CA143798 (to F.M.), the Susan G. Komen Foundation (to R.M.), Cellex Foundation (to V.A.), by Redes Tematicas de Investigacion en Cancer (RD12/0036/0055 to P.G. and E.A.), and the Breast Cancer Research Foundation (to K.P.). Part of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.",
year = "2014",
month = feb,
day = "13",
doi = "10.1016/j.celrep.2013.12.041",
language = "الإنجليزيّة",
volume = "6",
pages = "514--527",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}