Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer

• Project/Area Number: 15K10110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Kazuma Okamoto 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20285258)
• Co-Investigator(Kenkyū-buntansha): 市川 大輔 山梨大学, 大学院総合研究部, 教授 (20347446)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リキッドバイオプシー / 胃癌 / HER2 / バイオマーカー / 胃十二指腸外科学 / ddPCR / 遊離DNA

Outline of Final Research Achievements

Oncogenic activation (e.g. amplification) of uman epidermal growth factor receptor 2 (HER2) results in its protein overexpression and subsequent abnormal cell signalling, which contributes to cancer progression. Important issues for HER2-targeted therapy in GC are inaccurate assessments of HER2 status owing to intratumoral heterogeneity, which results in inappropriately choosing patients for HER2-targeted therapy. We investigated the potential clinical utility of the droplet digital PCR (ddPCR)-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress. The plasma HER2 amplification determined by ddPCR is a repeatable and noninvasive approach for real- time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence.

Research Products

• [Journal Article] Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer. (2017)
  • Author(s): Shoda K, Ichikawa D, Fujita Y, Masuda K, Hiramoto H, Hamada J, Arita T, Konishi H, Komatsu S, Shiozaki A, Kakihara N, Okamoto K, Taniguchi H, Imoto I, Otsuji E.
  • Journal Title: Gastric Cancer Volume: 1 Issue: 1 Pages: 126-135
  • DOI: 10.1007/s10120-016-0599-z
  • NAID: 40021062596
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical utility of circulating cell-free Epstein-Barr virus DNA in patients with gastric cancer. (2017)
  • Author(s): Shoda K, Ichikawa D, Fujita Y, Masuda K, Hiramoto H, Hamada J, Arita T, Konishi H, Kosuga T, Komatsu S, Shiozaki A, Okamoto K, Imoto I, Otsuji E.
  • Journal Title: Oncotarget Volume: 17 Issue: 17 Pages: 28796-28804
  • DOI: 10.18632/oncotarget.15675
  • NAID: 120006306639
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 胃癌ゲノム情報を考慮したtailor-made liquid biopsy (2018)
  • Author(s): Shoda K, Okamoto K, Ichikawa D, Fujita Y, Masuda K, Hiramoto H, Hamada J, Arita T, Konishi H, Komatsu S, Shiozaki A, Kakihara N, Taniguchi H, Imoto I, Otsuji E.
  • Organizer: 消化器外科学会
• [Presentation] Droplet digital PCRを用いた胃癌患者血漿遊離DNAにおけるHER2増幅モニタリング (2016)
  • Author(s): 庄田勝俊 市川大輔 岡本和真
  • Organizer: 消化器癌発生学会
  • Place of Presentation: 城山観光ホテル
  • Invited
• [Presentation] 末梢循環遊離DNAを用いた血漿 HER2 増幅診断法の開発と胃癌治療における有用性の検討 (2016)
  • Author(s): 市川大輔 岡本和真
  • Organizer: 日本外科学会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 胃癌患者循環遊離DNAを用いた新たな血漿HER2増幅診断法の開発と有用性の検討 (2015)
  • Author(s): 市川大輔
  • Organizer: 第２３回消化器関連学会週間
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2015-10-08