Study on the mechanism of imatinib-induced resistance in gastrointestinal stromal tumors.
- Author:
Yang ZHOU
1
;
Ying-yong HOU
;
Yun-shan TAN
;
Shao-hua LU
;
Jun HOU
;
Jing-lei LIU
;
Jing QIN
;
Kun-tang SHEN
;
Yi-hong SUN
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Antineoplastic Agents; therapeutic use; Benzamides; Codon; Drug Resistance, Neoplasm; Exons; Female; Follow-Up Studies; Gastrointestinal Stromal Tumors; drug therapy; genetics; pathology; surgery; Humans; Imatinib Mesylate; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Piperazines; therapeutic use; Protein-Tyrosine Kinases; antagonists & inhibitors; Proto-Oncogene Proteins c-kit; genetics; Pyrimidines; therapeutic use; Receptor, Platelet-Derived Growth Factor alpha; genetics
- From: Chinese Journal of Oncology 2009;31(8):597-601
- CountryChina
- Language:Chinese
-
Abstract:
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.
