کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2041872 1073176 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity
ترجمه فارسی عنوان
استنتاج تکامل تومور در طی شیمیدرمانی با استفاده از مدل سازی محاسباتی و تجزیه و تحلیل وضعیت ژنتیکی و تنوع سلولی فنوتیپی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Evolutionary dynamics during neoadjuvant chemotherapy in breast cancer
• Computational model to predict evolutionary trajectories and topologic patterns
• Intratumor heterogeneity measures predict response to treatment
• Changes in intratumor genetic and phenotypic diversity due to breast cancer therapy

SummaryCancer 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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 6, Issue 3, 13 February 2014, Pages 514–527
نویسندگان
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