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  • Title: Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case.
    Author: Utsunomiya T, Okamoto M, Yano S, Kameyama T, Matsuyama A, Kuma S, Yamamoto M, Fujiwara M, Ishida T.
    Journal: Surg Today; 2008; 38(1):65-7. PubMed ID: 18085368.
    Abstract:
    Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the c-kit receptor gene, which are targets for imatinib mesylate. However, imatinib resistance is an increasing clinical problem. We herein present such a case with a recurrent GIST, in association with the development of a secondary mutation in the c-kit gene. A 67-year-old man, who had a GIST of the stomach with multiple liver metastases, underwent a partial gastrectomy, distal pancreatectomy, and partial hepatectomy. After surgery, he was treated with imatinib. However, during the approximately 4-year treatment period, a recurrence of the GIST in the liver was detected, for which a partial hepatectomy was again performed. The primary GIST constitutively had a deletion mutation in exon 11. In addition, the recurrent hepatic tumor developed a secondary point mutation (Val654Ala) in exon 13, which may be responsible for the imatinib resistance.
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