Detection of circulating tumor DNA in cell-free DNA in gastric cancer patients and imatinib-resistant GIST patients using next-generation sequencer

• Project/Area Number: 26461977
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: Kurokawa Yukinori 大阪大学, 医学系研究科, 助教 (10470197)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ctDNA / 次世代シーケンサー / 胃癌 / GIST

Outline of Final Research Achievements

We investigated whether tumor-specific mutations could be detected in circulating tumor DNA (ctDNA) from the peripheral blood in patients with gastric cancer or imatinib-resistant GIST.
Cell-free DNA was extracted in blood samples in 6 patients with gastric cancer. Identical TP 53 mutations could be detected in ctDNA in 3 of the 6 patients. All 3 patients had extremely progressive disease, and the fraction rates of ctDNA were also consistent with tumor volume and disease course. Regarding GIST, imatinib-resistant lesions had single nucleotide substitutions in C-KIT exon 13 in three patients and exon 18 in one patient. Identical secondary C-KIT mutations could be detected in ctDNA with a mutant fraction range of 0.010- 9.385%, and the fraction rate of ctDNA was consistent with tumor volume and disease course.

Research Products

• [Journal Article] Detecting secondary c-KIT mutations in the peripheral blood of patients with imatinib-resistant gastrointestinal stromal tumor. (2016)
  • Author(s): Wada N, Kurokawa Y, Takahashi T, Hamakawa T, Hirota S, Naka T, Miyazaki Y, Makino T, Yamasaki M, Nakajima K, Takiguchi S, Mori M, Doki Y.
  • Journal Title: Oncology Volume: 90 Issue: 2 Pages: 112-117
  • DOI: 10.1159/000442948
  • Peer Reviewed
• [Journal Article] Monitoring gastric cancer progression with circulating tumour DNA (2015)
  • Author(s): Hamakawa T, Kukita Y, Kurokawa Y, Miyazaki Y, Takahashi T, Yamasaki M, Miyata H, Nakajima K, Taniguchi K, Takiguchi S, Mori M, Doki Y, Kato K
  • Journal Title: British Journal of Cancer Volume: 112 Issue: 2 Pages: 352-356
  • DOI: 10.1038/bjc.2014.609
  • Peer Reviewed / Open Access
• [Presentation] イマチニブ耐性GIST患者の末梢血におけるC-KITの変異検索 (2016)
  • Author(s): 和田範子、黒川幸典、高橋剛、宮崎安弘、牧野知紀、山崎誠、中島清一、瀧口修司、森正樹、土岐祐一郎
  • Organizer: 第71回日本消化器外科学会総会
  • Place of Presentation: 徳島
  • Year and Date: 2016-07-14