Establishment of Japan circulating tumor DNA cancer screening panel

2019 Fiscal Year Annual Research Report

• Project/Area Number: 18K15332
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: LOW SIEWKEE 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 研究員 (40634720)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: liquid biopsy / ctDNA / cell-free DNA / NGS

Outline of Annual Research Achievements

This proposal aims to establish customized NGS panels to detect circulating tumor DNA (ctDNA) from various solid tumors. Two panels were established: JFCR cfDNA screening panel for cancer screening and JFCR cfDNA actionable mutation panel for detection of variants with therapeutic implication.
With 2 commercial cfDNA controls, these panels detected mutations with limit of detection at 0.2%. The correlation r2 between the NGS data and control is 0.95.
JFCR screening panel is a 33 cancer gene panel, designed after assessing mutation profiles from TCGA and COSMIC databases. ctDNA detection rate varies among solid cancers and stages, range 50-67%.
JFCR cfDNA actionable mutation panel is a 59 gene panel that covers actionable mutations, CNV and fusions. The average ctDNA detection rate is 79%.

Research Products

• [Journal Article] Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants (2020)
  • Author(s): Shu Xiang、Long Jirong、Cai Qiuyin、et al.、Low Siew-Kee、et al.、Zheng Wei
  • Journal Title: Nature Communications Volume: 11 Pages: 1217
  • DOI: 10.1038/s41467-020-15046-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical significance of gene mutation in ctDNA analysis for hormone receptor-positive metastatic breast cancer. (2020)
  • Author(s): Tomoko Shibayama、Siew-Kee Low、Makiko Ono、Takayuki Kobayashi、Kokoro Kobayashi、Ippei Fukada、Yoshinori Ito、Takayuki Ueno、Shinji Ohno、Yusuke Nakamura、Shunji Takahashi
  • Journal Title: Breast Cancer Research and Treatment Volume: 180 Pages: 331-341
  • DOI: 10.1007/s10549-019-05512-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population (2019)
  • Author(s): Low Siew-Kee、Chin Yoon Ming、et al.、Nakamura Yusuke、Kubo Michiaki、Katagiri Toyomasa、Miki Yoshio
  • Journal Title: Scientific Reports Volume: 9 Pages: 17332
  • DOI: 10.1038/s41598-019-53654-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GWAS of five gynecologic diseases and cross-trait analysis in Japanese (2019)
  • Author(s): Masuda Tatsuo、Low Siew-Kee、Akiyama Masato、Hirata Makoto、Ueda Yutaka、Matsuda Koichi、Kimura Tadashi、Murakami Yoshinori、Kubo Michiaki、Kamatani Yoichiro、Okada Yukinori
  • Journal Title: European Journal of Human Genetics Volume: 28 Pages: 95～107
  • DOI: 10.1038/s41431-019-0495-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Next generation sequencing of circulating tumor DNA to monitor treatment response to CDK4/6 inhibitors in breast cancer. (2020)
  • Author(s): Yoon Ming Chin, Tomoko Shibayama, Masumi Otaki, Hiu Ting Chan, Makiko Ono, Yoshinori Ito, Shunji Takahashi, Shinji Ohno, Takayuki Ueno, Yusuke Nakamura, Siew-Kee Low
  • Organizer: Advances in liquid biopsy, American Association for Cancer Research
  • Int'l Joint Research
• [Presentation] Monitoring Osimertinib treatment response using circulating tumor DNA/RNA (2019)
  • Author(s): Siew-Kee Low, Ken Uchibori, Rie Hayashi, Yoon Ming Chin, Hiu Ting Chan, Satoru Kitazono, Noriko Yanagitani, Atsushi Horiike, Ryohei Katayama, Makoto Nishio and Yusuke Nakamura
  • Organizer: The 78th Annual Meeting of the Japanese Cancer Association
• [Presentation] Potential clinical application of circulating tumor DNA detection and monitoring in cancer management. (2019)
  • Author(s): Siew-Kee Low
  • Organizer: 6th C.MIC (Colegio Mexicano Para La Investigacion Del Cancer)
  • Invited