Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case.
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.
Utsunomiya
Tohru
T
Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima 730-8619, Japan.
Okamoto
Masahiro
M
Yano
Shuya
S
Kameyama
Toshihumi
T
Matsuyama
Ayumi
A
Kuma
Sosei
S
Yamamoto
Manabu
M
Fujiwara
Megumu
M
Ishida
Teruyoshi
T
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D001549:Benzamides; D004273:DNA, Neoplasm; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit