The genetic and immunohistochemical characteristics in imatinib-resistant gastrointestinal stromal tumor
10.3781/j.issn.1000-7431.2008.12.011
- Author:
Chun-Meng WANG
1
Author Information
1. Department of Abdominal Surgery
- Publication Type:Journal Article
- Keywords:
Drug resistance;
Gastrointestinal neoplasms;
Imatinib;
KIT gene
- From:
Tumor
2008;28(12):1064-1068
- CountryChina
- Language:Chinese
-
Abstract:
Objective: The application of the tyrosine kinase inhibitor imatinib changed the treatment style and the prognosis foreground of gastrointestinal stromal tumor (GIST). The prognosis of advanced GIST was improved significantly. However, the number of patients with imatinib resistance increased continuously with enlongation of treatment period. Imatinib resistance became a hot point recently. This study aimed to explore the mechanism responsible for the acquired resistance to imatinib. Methods: With the bidirectional DNA sequencing and the analysis of an ABI PRISM 310 capillary electrophoresis system, this work sequenced the extrons 9, 11, 13, and 17 of KIT gene and the extron 12 and 18 in platelet derived growth factor receptor (PDGFR) α gene in the 9 GIST patients who were resistant to imatinib or obtained stable disease (SD) during imatinib treatment. Results: Activating mutations of KIT gene existed in 7 of 9 cases of GIST patients. Six cases had the KIT gene mutation in exon 11 encoding the juxtamembrane domain and 1 case had mutation in exon 13. Secondary KIT mutations were identified in the 4 imatinib-resistant patients. This work found an identical novel missense mutation in exon 17, T2467T-→T2467G, which caused a substitution of Tyr by Asp at codon 823 (Y823 D) in tyrosine kinase domain of KIT. Conclusion: The imatinib resistance may be related with missense mutation in exon 17, T2467T→T2467G, in tyrosine kinase domain of KIT.
