2021 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 | ctDNA / liquid biopsy / NGS |
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| Outline of Annual Research Achievements |
Immune checkpoint inhibitor (ICI) is an effective treatment for various solid tumors, however, a significant proportion of patients do not respond to ICI. The current proposal aims to evaluate the usefulness of circulating tumor DNA (ctDNA) to identify patients who are most likely to respond to ICI. Several biomarkers and tumor mutational burden (TMB) were reported to correlate with better ICI outcome.
Hybrid capture ultradeep targeted sequencing was conducted with ctDNA extracted from advanced non-small cell lung cancer (NSCLC) using a panel that consist of >500 genes for blood TMB evaluation. The mean coverage is about 1800X. More than 500 SNV, MNV and indels were detected in 250 genes. About 65% of patients were categorized as bTMB-high by using the threshold value of >=10mut/Mb.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Before conducting experiment on clinical samples, other parameters such as linearity of depth in targeted region and molecular conversion rate of the panel were evaluated as quality control measurements using NGS standard control samples before using the panel on cancer patient's samples.
Bioinformatics pipeline including deduplicate and reads collapse using UMI algorithm were established to analyze the variants detected from this 500 gene panel using clinical samples from NSCLC.
The large panel was able to to evaluate bTMB, however, further refinement of variants calling from this panel will be necessary.
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| Strategy for Future Research Activity |
QC filtering has to be established to minimize systematic and sequencing errors in detecting genetic variants using a large panel.
Although the large panel is feasible to capture blood TMB, ctDNA detection remained challenging take into consideration of higher limit of detection at 0.5% with limited input of cell-free DNA from cancer patients. A relative smaller panel (100-150 genes) will be designed for the identification of specific biomarkers for ICI response.
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[Presentation] Liquid biopsy for precision oncology: Cutting edge technology meets personalized cancer management2021
Author(s)
SK Low, HT Chan, YM Chin, K Uchibori, R Ariyasu, T Shibayama, N Fukuda, J Tomomatsu, I Fukada, S Nagayama, T Ueno, M Nishio, S Takahashi, Y Nakamura
Organizer
The 80th Annual Meeting of the Japanese Cancer Association
Int'l Joint Research / Invited
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