Department of Nuclear Medicine, Rikshospitalet, Oslo University Hospital, 0027 Oslo, Norway.
Anticancer Res. 2009 Nov;29(11):4331-6.
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.
GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established.
The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient.
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.
大多数胃肠道间质瘤（GIST）含有致癌性 KIT（v-kit Hardy-Zuckerman 4 猫肉瘤病毒致癌基因同源物）或血小板衍生生长因子-α（PDGFRA）受体酪氨酸激酶（TK）突变，最初但仅暂时对 TK 抑制剂敏感。本研究旨在建立和鉴定一种可用于评估各种分子靶向治疗的人 GIST 异种移植物。
将来自四名患者的 GIST 组织植入无胸腺裸鼠的皮下。在一种情况下建立了肿瘤系。
异种移植物显示出特征性的 GIST 形态，并表现出与患者相同的突变谱。
已在裸鼠中建立并维持了携带 KIT 外显子 11 和 17 突变的人 GIST 异种移植物 3 年（13 代）。该模型将能够进一步研究耐药机制、联合治疗，并允许测试新的靶向治疗。
