Research Papers:
Patient-derived cell models as preclinical tools for genome-directed targeted therapy
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Abstract
Ji Yun Lee1,*, Sun Young Kim1,*, Charny Park1,*, Nayoung K.D. Kim2,*, Jiryeon Jang1, Kyunghee Park2, Jun Ho Yi7, Mineui Hong3,4, Taejin Ahn2, Oliver Rath5, Julia Schueler5, Seung Tae Kim1, In-Gu Do4, Sujin Lee1, Se Hoon Park1, Yong Ick Ji6, Dukwhan Kim6, Joon Oh Park1,3, Young Suk Park1, Won Ki Kang1, Kyoung-Mee Kim3,4, Woong-Yang Park2,6, Ho Yeong Lim1, Jeeyun Lee1,3
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Samsung Genome Institute, Samsung Medical Center, Seoul, Korea
3Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea
4Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
5Oncotest, Freiburg, Germany
6Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea
7Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, Korea
*These authors have contributed equally to this work
Correspondence to:
Ho Yeong Lim, e-mail: [email protected]
Jeeyun Lee, e-mail: [email protected]
Woong-Yang Park, e-mail: [email protected]
Keywords: gastric cancer, patient-derived cells, genomic analysis, targeted therapy
Received: February 15, 2015 Accepted: July 03, 2015 Published: July 16, 2015
ABSTRACT
Background: In this study, we established patient-derived tumor cell (PDC) models using tissues collected from patients with metastatic cancer and assessed whether these models could be used as a tool for genome-based cancer treatment.
Methods: PDCs were isolated and cultured from malignant effusions including ascites and pleural fluid. Pathological examination, immunohistochemical analysis, and genomic profiling were performed to compare the histological and genomic features of primary tumors, PDCs. An exploratory gene expression profiling assay was performed to further characterize PDCs.
Results: From January 2012 to May 2013, 176 samples from patients with metastatic cancer were collected. PDC models were successfully established in 130 (73.6%) samples. The median time from specimen collection to passage 1 (P1) was 3 weeks (range, 0.5–4 weeks), while that from P1 to P2 was 2.5 weeks (range, 0.5–5 weeks). Sixteen paired samples of genomic alterations were highly concordant between each primary tumor and progeny PDCs, with an average variant allele frequency (VAF) correlation of 0.878. We compared genomic profiles of the primary tumor (P0), P1 cells, P2 cells, and patient-derived xenografts (PDXs) derived from P2 cells and found that three samples (P0, P1, and P2 cells) were highly correlated (0.99–1.00). Moreover, PDXs showed more than 100 variants, with correlations of only 0.6–0.8 for the other samples. Drug responses of PDCs were reflective of the clinical response to targeted agents in selected patient PDC lines.
Conclusion(s): Our results provided evidence that our PDC model was a promising model for preclinical experiments and closely resembled the patient tumor genome and clinical response.
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