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2020 年度 実施状況報告書

Next generation sequencing of circulating tumor DNA to monitor treatment response to nivolumab in advanced gastric cancer

研究課題

研究課題/領域番号 20K07709
研究機関公益財団法人がん研究会

研究代表者

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)

研究期間 (年度) 2020-04-01 – 2023-03-31
キーワードliquid biopsy / ctDNA
研究実績の概要

The proposal aims to establish a customized circulating tumor DNA (ctDNA) cancer panel to evaluate the mutation profiles of cancer patients who receive immune checkpoint inhibitor (ICI).
Firstly, actionable mutations of cancer genes and genes related to ICI response were retrieved from literature review. The frequency of the hotspot mutations on these genes were assessed and incorporated into Ion AmpliSeq Designer.
The customized ctDNA panel was designed with the amplicon range 75-125bp with high specificity. The number of primer pools, amplicons inclusion and coverage of the panel were evaluated. The protocol of ultradeep targeted next sequencing (NGS) was designed to yield overall coverage of 50,000x using Ion S5 Prime system.

現在までの達成度 (区分)
現在までの達成度 (区分)

3: やや遅れている

理由

The customized ctDNA amplicon-based panel is designed. However, optimization is needed to increase the coverage and the specificity of the designed panel. Other parameters such as linearity of individual amplicon depth and molecular barcode tagging efficiency of the customized panel will also have to be evaluated as measurements of quality control by using NGS standard control samples before using the panel on cancer patient's samples.

今後の研究の推進方策

After the establishment and optimization of the customized ctDNA panel, ctDNA from serial sampling of cancer patients who receive ICI will be assessed. The efficacy and limit of detection of the customized panel will be evaluated.
Subsequently, mutations that are associated with the mechanism of resistance/non-responsive will be evaluated when patients encounter progression disease after receiving ICI treatment.

  • 研究成果

    (10件)

すべて 2020

すべて 雑誌論文 (6件) (うち国際共著 6件、 査読あり 6件、 オープンアクセス 4件) 学会発表 (4件) (うち国際学会 3件、 招待講演 1件)

  • [雑誌論文] Ultradeep targeted sequencing of circulating tumor DNA in plasma of early and advanced breast cancer2020

    • 著者名/発表者名
      Chin Yoon Ming、Takahashi Yoko、Chan Hiu Ting、Otaki Masumi、Fujishima Makoto、Shibayama Tomoko、Miki Yoshio、Ueno Takayuki、Nakamura Yusuke、Low Siew‐Kee
    • 雑誌名

      Cancer Science

      巻: 112 ページ: 454~464

    • DOI

      10.1111/cas.14697

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Clonal Hematopoiesis in Liquid Biopsy: From Biological Noise to Valuable Clinical Implications2020

    • 著者名/発表者名
      Chan Hiu Ting、Chin Yoon Ming、Nakamura Yusuke、Low Siew-Kee
    • 雑誌名

      Cancers

      巻: 12 ページ: 2277~2277

    • DOI

      10.3390/cancers12082277

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Plasma or Serum: Which Is Preferable for Mutation Detection in Liquid Biopsy?2020

    • 著者名/発表者名
      Pittella-Silva Fabio、Chin Yoon Ming、Chan Hiu Ting、Nagayama Satoshi、Miyauchi Eisaku、Low Siew-Kee、Nakamura Yusuke
    • 雑誌名

      Clinical Chemistry

      巻: 66 ページ: 946~957

    • DOI

      10.1093/clinchem/hvaa103

    • 査読あり / 国際共著
  • [雑誌論文] Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases2020

    • 著者名/発表者名
      Ishigaki Kazuyoshi、Akiyama Masato、Kanai Masahiro、Takahashi Atsushi、Kawakami Eiryo、Sugishita Hiroki、Sakaue Saori、Matoba Nana、Low Siew-Kee、et al., Nakamura Yusuke、Raychaudhuri Soumya、Inazawa Johji、Yamauchi Toshimasa、Kadowaki Takashi、Kubo Michiaki、Kamatani Yoichiro
    • 雑誌名

      Nature Genetics

      巻: 52 ページ: 669~679

    • DOI

      10.1038/s41588-020-0640-3

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Clinical significance of clonal hematopoiesis in the interpretation of blood liquid biopsy2020

    • 著者名/発表者名
      Chan Hiu Ting、Nagayama Satoshi、Chin Yoon Ming、Otaki Masumi、Hayashi Rie、Kiyotani Kazuma、Fukunaga Yosuke、Ueno Masashi、Nakamura Yusuke、Low Siew‐Kee
    • 雑誌名

      Molecular Oncology

      巻: 14 ページ: 1719~1730

    • DOI

      10.1002/1878-0261.12727

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Clinical significance of gene mutation in ctDNA analysis for hormone receptor-positive metastatic breast cancer2020

    • 著者名/発表者名
      Shibayama Tomoko、Low Siew-Kee、Ono Makiko、Kobayashi Takayuki、Kobayashi Kokoro、Fukada Ippei、Ito Yoshinori、Ueno Takayuki、Ohno Shinji、Nakamura Yusuke、Takahashi Shunji
    • 雑誌名

      Breast Cancer Research and Treatment

      巻: 180 ページ: 331~341

    • DOI

      10.1007/s10549-019-05512-5

    • 査読あり / 国際共著
  • [学会発表] Evaluation of Genexus system that automates specimen-to-report for cancer genomic profiling using liquid biopsy2020

    • 著者名/発表者名
      SK Low, K Uchibori, R Hayashi, HT Chan, R Ariyasu, S Kitazono, N Yanagitani, M Nishio and Y Nakamura.
    • 学会等名
      The 79th Annual Meeting of the Japanese Cancer Association
  • [学会発表] Evaluation of Genexus system that automates specimen-to-report for cancer genomic profiling within a day using liquid biopsy2020

    • 著者名/発表者名
      SK Low, K Uchibori, R Hayashi, HT Chan, R Ariyasu, S Kitazono, N Yanagitani, M Nishio and Y Nakamura
    • 学会等名
      American Society of Clinical Oncology (ASCO) Annual Meeting, 2020
    • 国際学会
  • [学会発表] NGS of circulating tumor DNA in clinical cancer research.2020

    • 著者名/発表者名
      SK Low, YM Chin, HT Chan, K Uchibori, S Nagayama, E Miyauchi, T Ueno, S Takahashi, M Nishio and Y Nakamura
    • 学会等名
      7th US-Japan Workshop on Biomarkers for Cancer Early Detection
    • 国際学会 / 招待講演
  • [学会発表] Next generation sequencing of circulating tumor DNA to monitor treatment response to CDK4/6 inhibitors in breast cancer.2020

    • 著者名/発表者名
      YM Chin, T Shibayama, M Otaki, HT Chan, M Ono, Y Ito, S Takahashi, S Ohno, T Ueno, Y Nakamura, SK Low
    • 学会等名
      Advances in liquid biopsy, American Association for Cancer Research (AACR)
    • 国際学会

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公開日: 2021-12-27  

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