• Zhonghua Zhong Liu Za Zhi · Aug 2009

    [Study on the mechanism of imatinib-induced resistance in gastrointestinal stromal tumors].

    • Yang Zhou, Ying-yong Hou, Yun-shan Tan, Shao-hua Lu, Jun Hou, Jing-lei Liu, Jing Qin, Kun-tang Shen, and Yi-hong Sun.
    • Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
    • Zhonghua Zhong Liu Za Zhi. 2009 Aug 1; 31 (8): 597-601.

    ObjectiveTo investigate the mechanism of imatinib mesylate (IM) induced-resistance in the patients with gastrointestinal stromal tumors (GISTs) and treated with imatinib.MethodsEight 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.ResultsIn 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.ConclusionThe 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.

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