Establishment of practical methods for next generation sequence from circulating tumor cells and circulating cell free DNA of oral cancer

• Project/Area Number: 15K15751
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: National Cancer Center Japan
• Principal Investigator: Honda Kazufumi 国立研究開発法人国立がん研究センター, その他部局等, ユニット長 (10260936)
• Co-Investigator(Kenkyū-buntansha): MORI Taisuke 国立研究開発法人国立がん研究センター, 中央病院, 医員 (00296708) ; YOSHIMOTO Seichi 国立研究開発法人国立がん研究センター, 中央病院, 科長 (00462242)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 末梢循環腫瘍細胞 / 口腔がん / バイオマーカー / ゲノム解析

Outline of Final Research Achievements

To select the optimal therapeutic strategy for individual patients with cancer, clarification of the biological behaviorof the tumor using minimal invasive methods is necessary. Circulating tumor cells (CTCs) and circulating cell-free DNA (ctDNA) released into the bloodstream from the primary tumor and metastases reflect the current tumor status. To establish a noninvasive method for identifying mutation status in tumor cells, we tried to develop methods for next-generation sequencing (NGS) from CTCs and ctDNA. CTCs were isolated using a cascading spiral system with patient blood (Hou et al, Scientific Rep. 2013) while ctDNA and DNA extracted from CTCs were analyzed by NGS (Ion PGM; LifeTechnology). Thirty-four patients with gastric, colorectal, esophageal, or head and neck cancers were enrolled in this study. A total of 8-77 CTCs/ml were retrieved from whole blood. Mutation profiles were successfully identified from CTCs and ctDNA obtained from each patient by NGS.

Research Products

• [Journal Article] Efficacy of adjuvant chemotherapy for non-small cell lung cancer assesed by metastatic potential assocaited with ACTN4 (2016)
  • Author(s): Miura N, Kamita M, Kakuya T, Fujiwara Y, Tsuta K, Shiraishi H, Takeshita F, Ochiya T, Hirokazu Shoji, Huang W, Ohe Y, Yamada T, Honda K
  • Journal Title: Oncotarget Volume: Apr 21 Issue: 22 Pages: 1-14
  • DOI: 10.18632/oncotarget.8890
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Patterns of recurrence after selective postoperative radiation therapy for patients with head and neck squamous cell carcinoma (2016)
  • Author(s): Murakami N, Matsumoto F, Yoshimoto S, Ito Y, Mori T, Ueno T, Tuchida K, Kashihara T, Kobayashi K, Harada K, Kitaguchi M, Sekii S, Umezawa R, Takahashi K, Inaba K, Igaki H, Itami J
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 192-195
  • DOI: 10.1186/s12885-016-2229-x
  • Peer Reviewed / Open Access
• [Journal Article] Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms. (2015)
  • Author(s): Honda K, Kobayashi M, Okusaka T, Rinaudo JA, Huang Y, Marsh T, Sanada M, Sasajima Y, Nakamori S, Shimahara M, Ueno T, Tsuchida A, Sata N, Ioka T, Yasunami Y, Kosuge T, Miura N, Kamita M, Sakamoto T, Shoji H, Jung G, Srivastava S, Yamada T.
  • Journal Title: Scientific Reports Volume: Nov 9;5 Issue: 1 Pages: 15921-15921
  • DOI: 10.1038/srep15921
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The biological role of actinin-4 (ACTN4) in malignant phenotypes of cancer. (2015)
  • Author(s): Honda K
  • Journal Title: Cell Biosci. Volume: Aug 18;5 Issue: 1 Pages: 41-49
  • DOI: 10.1186/s13578-015-0031-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Plasma biomarker for detection of early-stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII A2 isoforms (2016)
  • Author(s): Kazufumi Honda, Michimoto Kobayashi, Takuji Okusaka, Chigusa Morizane, Jo Ann Rinaudo, Ying Huang, Tracey Marsh, Shoji Nakamori, Masashi Shimahara, Takaaki Ueno, Akihiko Tsuchida, Naohiro Sata, Tatsuya Ioka, Tomoo Kosuge, Yohichi Yasunami, Masaru Yoshida, Ken Takeshi Azuma, Sudhir i Srivastava, Tesshi Yamada
  • Organizer: American Society Clinical Oncology (ASCO) Annual Meeting 2016
  • Place of Presentation: アメリカ
  • Year and Date: 2016-06-04
  • Int'l Joint Research
• [Presentation] Plasma biomarker for detection of early stage pancreatic cancer and risk factors for pancreatic malignancy using antibodies for apolipoprotein-AII isoforms (2016)
  • Author(s): Kazufumi Honda
  • Organizer: Japan US Workshop for Cancer Research
  • Place of Presentation: 日本
  • Year and Date: 2016-03-21
  • Int'l Joint Research / Invited
• [Presentation] Copy number of ACTN4 is a predictive indicator for late metastasis of cervical lymph nodes in early-stage tongue cancer (2015)
  • Author(s): Takanori Kakuya, Taisuke Mori, Yukio Watabe, Seichi Yoshimoto, Nami Miura, Takeshi Nomura, Tesshi Yamada, Huang Wilber, Takahiko Shibahara, Kazufumi Honda
  • Organizer: the International Conference on Oral and Maxillofacial Surgery 2015
  • Place of Presentation: オーストラリア
  • Year and Date: 2015-10-27
  • Int'l Joint Research
• [Presentation] Next generation sequencing of circulating tumor cells isolated from the peripheral blood and circulating free DNA of solid cancer patients. (2015)
  • Author(s): Tomohiko Kakizaki, Hirokazu Shoji, Koh Furuta, Ken Kato, Seiichi Yoshimoto, Fumihiko Matsumoto, Taisuke Mori, Tomohiro Sakuma, Tesshi Yamada, Chwee Teck Lim and Kazufumi Honda
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 愛知県
  • Year and Date: 2015-10-08
  • Int'l Joint Research