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. In addition, ultra-low pass whole genome sequencing was conducted to assess the tumor fraction from liquid biopsy. Whole exome sequencing of liquid biopsy with high tumor fraction was established and conducted to assess the potential clinical utilities of liquid biopsy, especially from patients who receive ICI.
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