title: High-fidelity of non-small cell lung cancer xenograft models derived from bronchoscopy-guided biopsies.
abstract: BACKGROUND
  At present, there are two main types of lung cancer xenograft models: those derived from stable cell lines, and patient-derived xenograft models established by surgically resected tissues. However, these animal models may not reflect the biological and genetic characteristics of advanced non-small cell lung cancer (NSCLC). We utilized bronchoscopy-guided biopsy tissues of NSCLC patients to establish xenograft models and analyzed their histopathologic and genotypic fidelity with parental tumors.
  
  
  METHODS
  Tumor tissues of NSCLC patients taken via bronchoscope were subcutaneously implanted into mice with non-obese diabetic-severe combined immunodeficiency disease for model establishment and serial passage. The histopathology and genotype of the samples from bronchoscopy-guided biopsy-derived xenograft (BDX) models and their parental tumors were detected.
  
  
  RESULTS
  Thirty BDXs out of 114 NSCLC patients (26.32%) were successfully established. Smoking status significantly affected the success rate of NSCLC BDX establishment (P = 0.010). The BDX establishment success rate in squamous cell cancer was higher than in adenocarcinoma, with no significant difference (32.00% vs. 16.21%, P = 0.112). However, the growth rate of passage 1 BDX was slower than that of passages 2 and 3. Almost all NSCLC BDXs maintained similarity to their parental tumor tissues in regard to histologic characteristics, pathological markers, and driver-gene mutations. Only one BDX model lost the epidermal growth factor receptor mutation contained in tumor parental tissue, as a result of heterogeneity.
  
  
  CONCLUSIONS
  NSCLC BDXs maintained high fidelity of histopathology and genotype with their original tumors. NSCLC BDXs that possess the actual status of advanced lung carcinoma should be used in preclinical research.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Fu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Duan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: An
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Thoracic Medical Oncology Peking University School of Oncology Beijing Cancer Hospital & Institute Beijing China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
keywords: Bronchoscopy; NSCLC; genotype; patient‐derived xenograft model
references.citation: Clin Lung Cancer. 2015 Jan;16(1):46-50
references.pmid: 25450875
references.citation: Clin Cancer Res. 2008 Oct 15;14(20):6456-68
references.pmid: 18927285
references.citation: J Clin Oncol. 2013 Feb 20;31(6):731-7
references.pmid: 23182986
references.citation: Lung Cancer. 2013 Aug;81(2):297-301
references.pmid: 23664446
references.citation: Am J Surg Pathol. 2003 Mar;27(3):311-24
references.pmid: 12604887
references.citation: Carcinogenesis. 2012 Sep;33(9):1797-805
references.pmid: 22696596
references.citation: J Transl Med. 2013 Jul 10;11:168
references.pmid: 23842453
references.citation: Cancer. 1995 Jan 1;75(1 Suppl):191-202
references.pmid: 8000996
references.citation: Nat Genet. 2011 Sep 25;43(11):1098-103
references.pmid: 21946351
references.citation: J Clin Oncol. 2009 Jun 1;27(16):2653-9
references.pmid: 19414683
references.citation: J Clin Oncol. 2014 Jan 10;32(2):121-8
references.pmid: 24323028
references.citation: Clin Cancer Res. 2011 Jan 1;17 (1):134-41
references.pmid: 21081655
references.citation: Eur J Cardiothorac Surg. 2011 Jul;40(1):e29-33
references.pmid: 21420313
references.citation: Cell. 2012 May 25;149(5):994-1007
references.pmid: 22608083
references.citation: Lancet Oncol. 2012 Mar;13(3):239-46
references.pmid: 22285168
references.citation: Neoplasia. 2013 Oct;15(10):1138-50
references.pmid: 24204193
references.citation: Cancer Res. 2009 Apr 15;69(8):3364-73
references.pmid: 19351829
references.citation: Transl Oncol. 2014 Dec;7(6):795-9
references.pmid: 25500090
references.citation: Science. 2004 Jun 4;304(5676):1497-500
references.pmid: 15118125
references.citation: Sci Transl Med. 2010 Dec 15;2(62):62ra93
references.pmid: 21160078
references.citation: Carcinogenesis. 2012 Jul;33(7):1270-6
references.pmid: 22510280
references.citation: Cancer Res. 2014 Feb 15;74(4):1272-83
references.pmid: 24356420
references.citation: Anticancer Res. 2014 Feb;34(2):735-44
references.pmid: 24511007
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11
references.pmid: 15329413
references.citation: J Thorac Oncol. 2014 Apr;9(4):549-53
references.pmid: 24736079
references.citation: Nat Rev Cancer. 2006 Jul;6(7):565-71
references.pmid: 16794639
references.citation: Ann Oncol. 2010 May;21 Suppl 5:v120-5
references.pmid: 20555060
references.citation: N Engl J Med. 2004 May 20;350(21):2129-39
references.pmid: 15118073
references.citation: PLoS One. 2015 Feb 23;10 (2):e0117333
references.pmid: 25706305
references.citation: Lancet Oncol. 2010 Feb;11(2):121-8
references.pmid: 20022809
references.citation: Eur J Cardiothorac Surg. 2009 Sep;36(3):454-9
references.pmid: 19502076
references.citation: J Thorac Oncol. 2013 Aug;8(8):e75-8
references.pmid: 23857406
references.citation: Lancet Oncol. 2011 Aug;12(8):735-42
references.pmid: 21783417
references.citation: Bioanalysis. 2011 Feb;3(4):383-9
references.pmid: 21338257
references.citation: J Clin Oncol. 2012 Sep 1;30(25):3077-83
references.pmid: 22826274
references.citation: Clin Cancer Res. 2003 Sep 15;9(11):4227-39
references.pmid: 14519650
references.citation: N Engl J Med. 2009 Sep 3;361(10):947-57
references.pmid: 19692680
references.citation: Clin Cancer Res. 2010 Feb 15;16(4):1324-30
references.pmid: 20145159
references.citation: Cell. 2014 Mar 13;156(6):1298-311
references.pmid: 24630729