title: Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.
abstract: BACKGROUND
  The majority of gastrointestinal stromal tumours (GISTs) contain oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK) mutations and are initially, but only temporarily sensitive to TK inhibitors. The aim of this study was to establish and characterize a human GIST xenograft that could be used for evaluating various molecularly targeted therapies.
  
  
  METHODS
  GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established.
  
  
  RESULTS
  The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient.
  
  
  CONCLUSIONS
  A human GIST xenograft with mutation in KIT exons 11 and 17 has been established and maintained in nude mice for 3 years (13 passages). This model will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.
authors.affiliation: Department of Nuclear Medicine, Rikshospitalet, Oslo University Hospital, 0027 Oslo, Norway. mona.elisabeth.revheim@radiumhospitalet.no
authors.forename: Mona-Elisabeth
authors.initials: ME
authors.lastname: Revheim
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Berner
authors.forename: Oyvind Sverre
authors.initials: OS
authors.lastname: Bruland
authors.forename: Kathrine
authors.initials: K
authors.lastname: Røe
authors.forename: Hege Oma
authors.initials: HO
authors.lastname: Ohnstad
authors.forename: Bodil
authors.initials: B
authors.lastname: Bjerkehagen
authors.forename: Tore
authors.initials: T
authors.lastname: Bach-Gansmo
mesh_terms: D000328:Adult; D000818:Animals; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D007621:Karyotyping; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha