2022 Fiscal Year Final Research 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 Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
LOW Siew Kee 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 / cell-free DNA / NGS / immunotherapy / tumor mutational burden |
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| Outline of Final Research Achievements |
The current proposal aimed to evaluate the clinical utilities of circulating tumor DNA (ctDNA) in immunotherapy responsiveness monitoring.
Low-pass whole genome sequencing revealed genome-wide copy number alterations (CNA) landscape reflecting tumor fraction in cfDNA. Our findings revealed higher tumor fraction correlating with high variant allele frequency (VAF) more than 10%, or with samples containing multiple mutations with a VAF less than 10% from blood cfDNA. Changes on CNA patterns in cfDNA during monitoring might reflect immunotherapy responsiveness.
Large 500 genes targeted panel for NGS allows the evaluation of blood tumor mutational burden. However, subset of mutations with VAF below the limit of detection (LOD) 0.5% were not detected. Several factors, including TMB evaluation, gene coverage, and LOD, should be considered when utilizing targeted sequencing for ctDNA detection in monitoring immunotherapy responsiveness.
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| Free Research Field |
cancer genetics
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| Academic Significance and Societal Importance of the Research Achievements |
Next generation sequencing of cell-free DNA including low-pass whole genome sequencing for genome-wide copy number alteration assessment and large panel targeted sequencing for blood tumor mutational burden evaluation might be useful for immunotherapy responsiveness monitoring.
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