دورية أكاديمية
Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma.
| العنوان: | Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma. |
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| المؤلفون: | Bolck HA; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Corrò C; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Kahraman A; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., von Teichman A; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Toussaint NC; NEXUS Personalized Health Technologies, ETH Zurich, Zurich, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland., Kuipers J; SIB Swiss Institute of Bioinformatics, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Chiovaro F; InSphero AG, Schlieren, Switzerland., Koelzer VH; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Pauli C; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Moritz W; InSphero AG, Schlieren, Switzerland., Bode PK; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Rechsteiner M; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland., Beerenwinkel N; SIB Swiss Institute of Bioinformatics, Basel, Switzerland; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Schraml P; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: Peter.Schraml@usz.ch., Moch H; Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland. |
| المصدر: | European urology focus [Eur Urol Focus] 2021 Jan; Vol. 7 (1), pp. 152-162. Date of Electronic Publication: 2019 Jun 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101665661 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2405-4569 (Electronic) Linking ISSN: 24054569 NLM ISO Abbreviation: Eur Urol Focus Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier B.V., [2015]- |
| مواضيع طبية MeSH: | Carcinoma, Renal Cell*/genetics , Kidney Neoplasms*/genetics, Biomarkers, Tumor ; Evolution, Molecular ; Genetic Heterogeneity ; Humans ; Precision Medicine |
| مستخلص: | Background: Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC). Objective: To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter- and intratumor heterogeneity. Design, Setting, and Participants: We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens. Outcome Measurements and Statistical Analysis: We confirmed the concordance of 2D and 3D patient-derived cell (PDC) models with the original tumor tissue in terms of histology, biomarker expression, cancer driver mutations, and copy number alterations. We addressed inter- and intrapatient heterogeneity by analyzing clonal dynamics during serial passaging. Results and Limitations: In-depth genetic characterization verified the presence of heterogeneous cell populations, and revealed a high degree of similarity between subclonal compositions of monolayer and organoid cell cultures and the corresponding parental ccRCCs. Clonal dynamics were evident during serial passaging of cells in vitro, suggesting that PDC cultures can offer insights into evolutionary potential and treatment susceptibility of ccRCC subclones in vivo. Proof-of-concept drug profiling using selected ccRCC-targeted therapy agents highlighted patient-specific vulnerabilities in PDC models that could not be anticipated by interrogating commercially available cell lines. Conclusions: We demonstrate that PDC models mirror inter- and intratumor heterogeneity of ccRCC in vitro. Based on our findings, we envision that the use of these models will advance our understanding of the trajectories that cause genetic diversity and their consequences for treatment on an individual level. Patient Summary: In this study, we developed two- and three-dimensional patient-derived models from clear cell renal cell carcinoma (ccRCC) as "mini-tumors in a dish." We show that these cell models retain important features of the human ccRCCs such as the profound tumor heterogeneity, thus highlighting their importance for cancer research and precision medicine. (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Clonal dynamics; Patient-derived models; Personalized medicine; Renal cancer; Tumor heterogeneity |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20190704 Date Completed: 20220325 Latest Revision: 20220325 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.euf.2019.06.009 |
| PMID: | 31266731 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 2405-4569 |
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| DOI: | 10.1016/j.euf.2019.06.009 |