| 研究課題/領域番号 |
20K07709
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| 研究機関 | 公益財団法人がん研究会 |
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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)
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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| キーワード | ctDNA / liquid biopsy / NGS |
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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