Zhou Yang, Hou Ying-yong, Tan Yun-shan, Lu Shao-hua, Hou Jun, Liu Jing-lei, Qin Jing, Shen Kun-tang, Sun Yi-hong
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Zhong Liu Za Zhi. 2009 Aug;31(8):597-601.
To investigate the mechanism of imatinib mesylate (IM) induced-resistance in the patients with gastrointestinal stromal tumors (GISTs) and treated with imatinib.
Eight patients with GIST treated with IM developed secondary IM resistance. A total of 16 tumor samples (pre-IM therapy) and 11 tumor samples (post-IM treatment) were available. Exon 9, 11, 13, and 17 of c-kit gene as well as exon 12 and exon 18 of PDGFRA gene were sequenced.
In addition to the changes of baseline genotype, the IM-induced gene changes were concentrated in the kinase domain of c-kit gene in all 8 patients, 2 of them were located in the exon 13 of c-kit gene presenting with V654A, while 6 in exon 17 involving 816 and 820 to 823 codons.
The mechanism of imatinib mesylate resistance after initial treatment with this agent in gastrointestinal stromal tumors is a novel mutation development in kinase domain of c-kit.
探讨甲磺酸伊马替尼（IM）治疗胃肠间质瘤（GISTs）患者时诱导耐药的机制。
8例接受IM治疗的GIST患者出现继发性IM耐药。共获得16份肿瘤样本（IM治疗前）和11份肿瘤样本（IM治疗后）。对c-kit基因的第9、11、13和17外显子以及血小板衍生生长因子受体α（PDGFRA）基因的第12和18外显子进行测序。
除基线基因型改变外，所有8例患者中IM诱导的基因改变均集中在c-kit基因的激酶结构域，其中2例位于c-kit基因的第13外显子，表现为V654A，6例位于第17外显子，涉及816和820至823密码子。
胃肠间质瘤患者初次使用甲磺酸伊马替尼治疗后出现耐药的机制是c-kit激酶结构域发生新的突变。
