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

Publication ,  Journal Article
Almendro, V; Cheng, Y-K; Randles, A; Itzkovitz, S; Marusyk, A; Ametller, E; Gonzalez-Farre, X; Muñoz, M; Russnes, HG; Helland, A; Rye, IH ...
Published in: Cell reports
February 2014

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.

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Published In

Cell reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

February 2014

Volume

6

Issue

3

Start / End Page

514 / 527

Related Subject Headings

  • Phenotype
  • Models, Biological
  • Humans
  • Genotype
  • Genetic Variation
  • Genetic Heterogeneity
  • Female
  • Cell Proliferation
  • Breast Neoplasms
  • Antineoplastic Agents
 

Citation

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Almendro, V., Cheng, Y.-K., Randles, A., Itzkovitz, S., Marusyk, A., Ametller, E., … Polyak, K. (2014). Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Reports, 6(3), 514–527. https://doi.org/10.1016/j.celrep.2013.12.041
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): 514–27. https://doi.org/10.1016/j.celrep.2013.12.041.
Almendro V, Cheng Y-K, Randles A, Itzkovitz S, Marusyk A, Ametller E, et al. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell reports. 2014 Feb;6(3):514–27.
Almendro, Vanessa, et al. “Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.Cell Reports, vol. 6, no. 3, Feb. 2014, pp. 514–27. Epmc, doi:10.1016/j.celrep.2013.12.041.
Almendro 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. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell reports. 2014 Feb;6(3):514–527.
Journal cover image

Published In

Cell reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

February 2014

Volume

6

Issue

3

Start / End Page

514 / 527

Related Subject Headings

  • Phenotype
  • Models, Biological
  • Humans
  • Genotype
  • Genetic Variation
  • Genetic Heterogeneity
  • Female
  • Cell Proliferation
  • Breast Neoplasms
  • Antineoplastic Agents