Patient-derived cell models as preclinical tools for genomedirected targeted therapy

Ji Yun Lee, Sun Young Kim, Charny Park, Nayoung K.D. Kim, Jiryeon Jang, Kyunghee Park, Jun Ho Yi, Mineui Hong, Taejin Ahn, Oliver Rath, Julia Schueler, Seung Tae Kim, In Gu Do, Sujin Lee, Se Hoon Park, Yong Ick Ji, Dukwhan Kim, Joon Oh Park, Young Suk Park, Won Ki KangKyoung Mee Kim, Woong Yang Park, Ho Yeong Lim, Jeeyun Lee

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27 Scopus citations

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.

Original languageEnglish
Pages (from-to)25619-25630
Number of pages12
JournalOncotarget
Volume6
Issue number28
DOIs
StatePublished - 1 Jan 2015

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Keywords

  • Gastric cancer
  • Genomic analysis
  • Patient-derived cells
  • Targeted therapy

Cite this

Lee, J. Y., Kim, S. Y., Park, C., Kim, N. K. D., Jang, J., Park, K., Yi, J. H., Hong, M., Ahn, T., Rath, O., Schueler, J., Kim, S. T., Do, I. G., Lee, S., Park, S. H., Ji, Y. I., Kim, D., Park, J. O., Park, Y. S., ... Lee, J. (2015). Patient-derived cell models as preclinical tools for genomedirected targeted therapy. Oncotarget, 6(28), 25619-25630. https://doi.org/10.18632/oncotarget.4627