Murine model of gastrointestinal stromal tumors harboring a germline Kit K641E oncogenic mutant

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST. A mouse model of harboring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum in the knock-in Kit K641E murine GIST model by microarray. Microarray analysis was performed on antral tissue from three pairs of KitK641E:Neo/K641E:Neo and KitWT/WT P14 littermates. Antrum labeled RNAs were hybridized to MEEBO arrays containing on average 38784 mouse 70mer oligonucleotide probes (Stanford University, US).

胃肠道间质瘤（Gastrointestinal stromal tumors, GIST）被认为起源于卡哈尔间质细胞（interstitial cells of Cajal, ICC）或其前体细胞。绝大多数胃肠道间质瘤均存在受体酪氨酸激酶KIT（receptor tyrosine kinase KIT）的致癌突变。KIT K642E突变最初于散发性胃肠道间质瘤中被鉴定，后续又在家族性胃肠道间质瘤患者的生殖系样本中被检出。研究人员构建了携带生殖系Kit K641E突变的小鼠模型，以模拟家族性胃肠道间质瘤的发病进程。本研究通过基因芯片（microarray）技术，对该Kit K641E敲入小鼠胃肠道间质瘤模型的胃窦组织开展表达谱分析：实验选取3对KitK641E:Neo/K641E:Neo与KitWT/WT基因型的出生后第14天（P14）同窝小鼠的胃窦组织，将标记后的胃窦RNA与平均包含38784条小鼠70聚体寡核苷酸探针的MEEBO阵列（MEEBO arrays，美国斯坦福大学研发）进行杂交实验。