title: Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer.
abstract: Molecular annotated patient-derived xenograft (PDX) models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. We established 23 PDXs from 88 surgical specimens of lung cancer patients and determined gene mutations in these PDXs and their paired primary tumors by ultradeep exome sequencing on 202 cancer-related genes. The numbers of primary tumors with deleterious mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 43.5%, 21.7%, 17.4%, 17.4%, 13.0%, and 8.7%, respectively. Other genes with deleterious mutations in ≥3 (13.0%) primary tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1. Of 315 mutations detected in the primary tumors, 293 (93%) were also detected in their corresponding PDXs, indicating that PDXs have the capacity to recapitulate the mutations in primary tumors. Nevertheless, a substantial number of mutations had higher allele frequencies in the PDXs than in the primary tumors, or were not detectable in the primary tumor, suggesting the possibility of tumor cell enrichment in PDXs or heterogeneity in the primary tumors. The molecularly annotated PDXs generated from this study could be useful for future translational studies.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Hao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Head/Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Mengru
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Apar
authors.initials: A
authors.lastname: Pataer
authors.affiliation: Department of Thoracic and Head/Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Agda Karina
authors.initials: AK
authors.lastname: Eterovic
authors.affiliation: Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Qingxiu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kenna R
authors.initials: KR
authors.lastname: Shaw
authors.affiliation: Department of Bioinformatics and Computation Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Futreal
authors.affiliation: Department of Lymphoma, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Hofstetter
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rice
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Sepesi
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ara
authors.initials: A
authors.lastname: Vaporciyan
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Garrett L
authors.initials: GL
authors.lastname: Walsh
authors.affiliation: Department of Thoracic and Head/Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.
authors.forename: Faye M
authors.initials: FM
authors.lastname: Johnson
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA. Electronic address: bfang@mdanderson.org.
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009154:Mutation; D010105:Oxygenases
chemical_list: D014408:Biomarkers, Tumor; D010105:Oxygenases; C114415:nitric oxide dioxygenase
keywords: Biomarkers; Gene mutations; Lung cancer; Patient-derived xenografts; Tumor models