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J. Clin. Med. 2019, 8(4), 455; https://doi.org/10.3390/jcm8040455

New Chondrosarcoma Cell Lines with Preserved Stem Cell Properties to Study the Genomic Drift During In Vitro/In Vivo Growth

1
University Central Hospital of Asturias—Health and Research Institute of Asturias (ISPA), 33011 Oviedo, Spain
2
University Institute of Oncology of Asturias, 33011 Oviedo, Spain
3
CIBER in Oncology (CIBERONC), 28029 Madrid, Spain
4
Disease Research and Medicine (DREAMgenics) S.L., 33011 Oviedo, Spain
5
Department of Radiology of the Servicio de Radiología of the University Central Hospital of Asturias, 33011 Oviedo, Spain
6
Department of Medical Oncology of the Servicio de Radiología of the University Central Hospital of Asturias, 33011 Oviedo, Spain
7
Department of Pathology of the Servicio de Radiología of the University Central Hospital of Asturias, 33011 Oviedo, Spain
8
Department of Traumatology of the University Central Hospital of Asturias, 33011 Oviedo, Spain
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
Received: 4 March 2019 / Revised: 28 March 2019 / Accepted: 1 April 2019 / Published: 4 April 2019
(This article belongs to the Special Issue Cutting Edge Preclinical Models in Translational Medicine)
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Abstract

For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17). These lines displayed cancer stem cell-related and invasive features and were able to initiate subcutaneous and/or orthotopic animal models. Different mutations in Isocitrate Dehydrogenase-1 (IDH1), Isocitrate Dehydrogenase-2 (IDH2), and Tumor Supressor P53 (TP53) and deletion of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) were detected both in cell lines and tumor samples. In addition, other mutations in TP53 and the amplification of Mouse Double Minute 2 homolog (MDM2) arose during cell culture in CDS17 cells. Whole exome sequencing analysis of CDS17, T-CDS17, and matched patient samples confirmed that cell lines kept the most relevant mutations of the tumor, uncovered new mutations and revealed structural variants that emerged during in vitro/in vivo growth. Altogether, this work expanded the panel of clinically and genetically-annotated chondrosarcoma lines amenable for in vivo studies and cancer stem cell (CSC) characterization. Moreover, it provided clues of the genetic drift of chondrosarcoma cells during the adaptation to grow conditions. View Full-Text
Keywords: chondrosarcoma; primary cell lines; cancer stem cells; whole exome sequencing; genomic drift; animal model; cancer preclinical model chondrosarcoma; primary cell lines; cancer stem cells; whole exome sequencing; genomic drift; animal model; cancer preclinical model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rey, V.; Menendez, S.T.; Estupiñan, O.; Rodriguez, A.; Santos, L.; Tornin, J.; Martinez-Cruzado, L.; Castillo, D.; Ordoñez, G.R.; Costilla, S.; Alvarez-Fernandez, C.; Astudillo, A.; Braña, A.; Rodriguez, R. New Chondrosarcoma Cell Lines with Preserved Stem Cell Properties to Study the Genomic Drift During In Vitro/In Vivo Growth. J. Clin. Med. 2019, 8, 455.

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