Medical Oncology

, 30:522 | Cite as

Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors

  • Jing Gao
  • Ye Tian
  • Jian Li
  • Naiping Sun
  • Jiajia Yuan
  • Lin Shen
Original Paper


The aim of this study was to investigate the associations between secondary mutations of c-KIT/PDGFRα and acquired imatinib resistance or efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors (GISTs). Mutations of c-KIT (exons 9, 11, 13, 14, 17, and 18) and PDGFRα (exons 12 and 18) in tumor samples of 50 patients were analyzed by direct sequencing. A total of 50 samples before imatinib and 52 samples after imatinib were collected. Among 52 samples after imatinib, 38 samples were imatinib resistant and 14 samples were imatinib sensitive. All patients before imatinib treatment had primary mutations of c-KIT exon 11 (n = 45) or exon 9 (n = 5), and no PDGFRα mutations were found in these patients. After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. In our study, 19 patients received sunitinib treatment after the failure of imatinib, and it seemed that the median progression-free survival (7 vs. 19 months, P = 0.244) in patients with secondary mutations (n = 13) was lower than that in patients without secondary mutations (n = 6). Secondary mutations of c-KIT were significantly associated with acquired resistance to imatinib in Chinese GIST patients, and whether secondary mutations of c-KIT could influence the efficacy of sunitinib needed to be further investigated.


c-KIT Secondary mutation Acquired resistance Imatinib Sunitinib 



This work was supported by Beijing Municipal Natural Science Foundation (No. 7122031). We thank Dr. Jiping Yue (Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon, France) and Professor Sonya W Song (Clinical Research Laboratory of Peking University Cancer Hospital and Institute, Beijing, China) for critical reading of this manuscript.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jing Gao
    • 1
  • Ye Tian
    • 1
  • Jian Li
    • 1
  • Naiping Sun
    • 1
  • Jiajia Yuan
    • 1
  • Lin Shen
    • 1
  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of GI OncologyPeking University Cancer Hospital and InstituteHaidian District, BeijingChina

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