Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.
Mona Elisabeth Revheima b, Therese Seierstadc, Jeanne‐Marie Bernerb, Øyvind Sverre Brulandd, Kathrine Røeb, Hege Oma Ohnstadb, Bodil Bjerkehagenb, Tore Bach‐Gansmoe f
- aDepartment of Nuclear Medicine, Rikshospitalet, Oslo University Hospital, 0027 Oslo, Norway. mona.elisabeth.revheim@radiumhospitalet.no
- bUniversity of Oslo#TAB#
- cInstitute for Cancer Research
- dOncology
- eUniversity of Bergen
- fUniversity of Oslo
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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. MATERIALS AND 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. CONCLUSION: 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.