Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity
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-...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101428 |
| _version_ | 1811068948523778048 |
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| author | Almendro, Vanessa Cheng, Yu-Kang Randles, Amanda Itzkovitz, Shalev Marusyk, Andriy Ametller, Elisabet Gonzalez-Farre, Xavier Russnes, Hege G. Rye, Inga H. Borresen-Dale, Anne-Lise Maruyama, Reo van Oudenaarden, Alexander Dowsett, Mitchell Jones, Robin L. Reis-Filho, Jorge Gascon, Pere Michor, Franziska Polyak, Kornelia Munoz, Montse Helland, Aslaug Gonen, Mithat van Oudenaarden, Alexander |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Almendro, Vanessa Cheng, Yu-Kang Randles, Amanda Itzkovitz, Shalev Marusyk, Andriy Ametller, Elisabet Gonzalez-Farre, Xavier Russnes, Hege G. Rye, Inga H. Borresen-Dale, Anne-Lise Maruyama, Reo van Oudenaarden, Alexander Dowsett, Mitchell Jones, Robin L. Reis-Filho, Jorge Gascon, Pere Michor, Franziska Polyak, Kornelia Munoz, Montse Helland, Aslaug Gonen, Mithat van Oudenaarden, Alexander |
| author_sort | Almendro, Vanessa |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:03:19Z |
| format | Article |
| id | mit-1721.1/101428 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:03:19Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1014282022-09-23T10:34:46Z Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity Almendro, Vanessa Cheng, Yu-Kang Randles, Amanda Itzkovitz, Shalev Marusyk, Andriy Ametller, Elisabet Gonzalez-Farre, Xavier Russnes, Hege G. Rye, Inga H. Borresen-Dale, Anne-Lise Maruyama, Reo van Oudenaarden, Alexander Dowsett, Mitchell Jones, Robin L. Reis-Filho, Jorge Gascon, Pere Michor, Franziska Polyak, Kornelia Munoz, Montse Helland, Aslaug Gonen, Mithat van Oudenaarden, Alexander Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Physics Koch Institute for Integrative Cancer Research at MIT Itzkovitz, Shalev van Oudenaarden, Alexander 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. National Cancer Institute (U.S.). Physical Sciences Oncology Center (U54CA143874) 2016-03-03T02:47:43Z 2016-03-03T02:47:43Z 2014-01 2013-11 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/101428 Almendro, Vanessa, Yu-Kang Cheng, Amanda Randles, Shalev Itzkovitz, Andriy Marusyk, Elisabet Ametller, Xavier Gonzalez-Farre, et al. “Inference of Tumor Evolution During Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity.” Cell Reports 6, no. 3 (February 2014): 514–527. en_US http://dx.doi.org/10.1016/j.celrep.2013.12.041 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Almendro, Vanessa Cheng, Yu-Kang Randles, Amanda Itzkovitz, Shalev Marusyk, Andriy Ametller, Elisabet Gonzalez-Farre, Xavier Russnes, Hege G. Rye, Inga H. Borresen-Dale, Anne-Lise Maruyama, Reo van Oudenaarden, Alexander Dowsett, Mitchell Jones, Robin L. Reis-Filho, Jorge Gascon, Pere Michor, Franziska Polyak, Kornelia Munoz, Montse Helland, Aslaug Gonen, Mithat van Oudenaarden, Alexander Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title_full | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title_fullStr | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title_full_unstemmed | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title_short | Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity |
| title_sort | inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity |
| url | http://hdl.handle.net/1721.1/101428 |
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