Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor

Noriko Wada, Yukinori Kurokawa, Tsuyoshi Takahashi, Takuya Hamakawa, Seiichi Hirota, Tetsuji Naka, Yasuhiro Miyazaki, Tomoki Makino, Makoto Yamasaki, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

Objective: Imatinib is a standard treatment for metastatic gastrointestinal stromal tumor (GIST). Imatinib resistance is mostly caused by secondary mutations in C-KIT. The antitumor effect of second-line agents is correlated with the type of secondary mutation: indeed, sunitinib is effective against tumors with C-KIT exon 13 or 14 mutations. We investigated whether secondary C-KIT mutations can be detected in circulating tumor DNA (ctDNA) from peripheral blood. Methods: This study included 4 patients who underwent resection of imatinib-resistant GIST. Tumor-specific mutations in each tumor were determined by Sanger sequencing. ctDNA was extracted from peripheral blood obtained before and after the treatment of imatinib-resistant lesions. Each of the secondary target mutations in ctDNA was investigated, using a next-generation sequencer. Results: Imatinib-resistant lesions had single-nucleotide substitutions in C-KIT exon 13 in 3 patients and exon 18 in 1 patient. Identical secondary C-KIT mutations could be detected in ctDNA with a mutant fraction range of 0.010-9.385%. One patient had growth of an imatinib-resistant tumor containing a C-KIT exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. Conclusion: Detection of secondary C-KIT mutations in ctDNA could be useful for the selection of targeted agents and prediction of antitumor effects.

本文言語英語
ページ(範囲)112-117
ページ数6
ジャーナルOncology (Switzerland)
90
2
DOI
出版ステータス出版済み - 2 1 2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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