title: Development and characterization of a human orthotopic neuroblastoma xenograft.
abstract: Neuroblastoma is a pediatric cancer of the developing sympathoadrenal lineage. The tumors are known to develop from the adrenal gland or paraspinal ganglia and have molecular and cellular features of sympathetic neurons such as dense core vesicles and catecholamine production. Here we present the detailed molecular, cellular, genetic and epigenetic characterization of an orthotopic xenograft derived from a high-risk stage 4 neuroblastoma patient. Overall, the xenografted tumor retained the high risk features of the primary tumor and showed aggressive growth and metastasis in the mouse. Also, the genome was preserved with no additional copy number variations, structural variations or aneuploidy. There were 13 missense mutations identified in the xenograft that were not present in the patient's primary tumor and there were no new nonsense mutations. None of the missense mutations acquired in the xenograft were in known cancer genes. We also demonstrate the feasibility of using the orthotopic neuroblastoma xenograft to test standard of care chemotherapy and molecular targeted therapeutics. Finally, we optimized a new approach to produce primary cultures of the neuroblastoma xenografts for high-throughput drug screening which can be used to test new combinations of therapeutic agents for neuroblastoma.
authors: Department of Developmental Neurobiology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Elizabeth
authors: E
authors: Stewart
authors: Department of Chemical Biology and Therapeutics, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Anang
authors: A
authors: Shelat
authors: Department of Developmental Neurobiology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Cori
authors: C
authors: Bradley
authors: Department of Computational Biology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Xiang
authors: X
authors: Chen
authors: Department of Oncology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Sara
authors: S
authors: Federico
authors: Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Suresh
authors: S
authors: Thiagarajan
authors: Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Abbas
authors: A
authors: Shirinifard
authors: Department of Pathology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Armita
authors: A
authors: Bahrami
authors: Department of Oncology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Alberto
authors: A
authors: Pappo
authors: Department of Computational Biology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: Chunxu
authors: C
authors: Qu
authors: Department of Computational Biology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA.
authors: David
authors: D
authors: Finkelstein
authors: Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Andras
authors: A
authors: Sablauer
authors: Department of Developmental Neurobiology, St. Jude Children׳s Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: michael.dyer@stjude.org.
authors: Michael A
authors: MA
authors: Dyer
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D057166:High-Throughput Screening Assays; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases