2020 Fiscal Year Research-status Report
Next generation sequencing of circulating tumor DNA to monitor treatment response to nivolumab in advanced gastric cancer
| Project/Area Number |
20K07709
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| Research Institution | Japanese Foundation for Cancer Research |
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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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | liquid biopsy / ctDNA |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
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.
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| Strategy for Future Research Activity |
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.
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[Presentation] Next generation sequencing of circulating tumor DNA to monitor treatment response to CDK4/6 inhibitors in breast cancer.2020
Author(s)
YM Chin, T Shibayama, M Otaki, HT Chan, M Ono, Y Ito, S Takahashi, S Ohno, T Ueno, Y Nakamura, SK Low
Organizer
Advances in liquid biopsy, American Association for Cancer Research (AACR)
Int'l Joint Research
