title: Patient-derived cell models as preclinical tools for genome-directed targeted therapy.
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.
  
  
  CONCLUSIONS
  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.
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Ji Yun
authors: JY
authors: Lee
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Sun Young
authors: SY
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Charny
authors: C
authors: Park
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors: Nayoung K D
authors: NK
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Jiryeon
authors: J
authors: Jang
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors: Kyunghee
authors: K
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, Korea.
authors: Jun Ho
authors: JH
authors: Yi
authors: Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.|Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Mineui
authors: M
authors: Hong
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors: Taejin
authors: T
authors: Ahn
authors: Oncotest, Freiburg, Germany.
authors: Oliver
authors: O
authors: Rath
authors: Oncotest, Freiburg, Germany.
authors: Julia
authors: J
authors: Schueler
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Seung Tae
authors: ST
authors: Kim
authors: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: In-Gu
authors: IG
authors: Do
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Sujin
authors: S
authors: Lee
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Se Hoon
authors: SH
authors: Park
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Yong Ick
authors: YI
authors: Ji
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Dukwhan
authors: D
authors: Kim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.
authors: Joon Oh
authors: JO
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Young Suk
authors: YS
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Won Ki
authors: WK
authors: Kang
authors: Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.|Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Kyoung-Mee
authors: KM
authors: Kim
authors: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.|Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Woong-Yang
authors: WY
authors: Park
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Ho Yeong
authors: HY
authors: Lim
authors: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea.
authors: Jeeyun
authors: J
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001202:Ascitic Fluid / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D016066:Pleural Effusion, Malignant / Q000473:pathology; D057285:Precision Medicine; D011237:Predictive Value of Tests; D061251:Primary Cell Culture; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: gastric cancer; genomic analysis; patient-derived cells; targeted therapy