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

Abstract

Objective: To investigate the mechanism of imatinib mesylate (IM) induced-resistance in the patients with gastrointestinal stromal tumors (GISTs) and treated with imatinib.

Methods: 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.

Results: 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.

Conclusion: 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.