title: [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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ying-yong
authors.initials: YY
authors.lastname: Hou
authors.forename: Yun-shan
authors.initials: YS
authors.lastname: Tan
authors.forename: Shao-hua
authors.initials: SH
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Jing-lei
authors.initials: JL
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Kun-tang
authors.initials: KT
authors.lastname: Shen
authors.forename: Yi-hong
authors.initials: YH
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D003062:Codon; D019008:Drug Resistance, Neoplasm; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D003062:Codon; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha