[Study on the mechanism of imatinib-induced resistance in gastrointestinal stromal tumors].
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.
Zhou
Yang
Y
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Hou
Ying-yong
YY
Tan
Yun-shan
YS
Lu
Shao-hua
SH
Hou
Jun
J
Liu
Jing-lei
JL
Qin
Jing
J
Shen
Kun-tang
KT
Sun
Yi-hong
YH
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
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