Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.
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.
Revheim
Mona-Elisabeth
ME
Department of Nuclear Medicine, Rikshospitalet, Oslo University Hospital, 0027 Oslo, Norway. mona.elisabeth.revheim@radiumhospitalet.no
Seierstad
Therese
T
Berner
Jeanne-Marie
JM
Bruland
Oyvind Sverre
OS
Røe
Kathrine
K
Ohnstad
Hege Oma
HO
Bjerkehagen
Bodil
B
Bach-Gansmo
Tore
T
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*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha