Ya-Sian Chang1,2,3,4, Hsin-Yuan Fang5, Yao-Ching Hung6, Tao-Wei Ke7, Chieh-Min Chang8,9, Ting-Yuan Liu9, Yu-Chia Chen9, Dy-San Chao8,9, Hsi-Yuan Huang8,9, Jan-Gowth Chang10,8,9,11,12. 1. Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan, Republic of China. d6781@mail.cmuh.org.tw. 2. Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China. d6781@mail.cmuh.org.tw. 3. Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China. d6781@mail.cmuh.org.tw. 4. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, Republic of China. d6781@mail.cmuh.org.tw. 5. Department of Thoracic Surgery, China Medical University Hospital, Taichung, Taiwan, Republic of China. 6. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan, Republic of China. 7. Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan, Republic of China. 8. Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China. 9. Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China. 10. Epigenome Research Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan, Republic of China. 11. School of Medicine, China Medical University, Taichung, Taiwan, Republic of China. 12. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, Republic of China.
Abstract
PURPOSE: Analysis of circulating tumor DNA (ctDNA) offers an unbiased and noninvasive way to assess the genetic profiles of tumors. This study aimed to analyze mutations in ctDNA and their correlation with tissue mutations in patients with a variety of cancers. METHODS: We included 21 cancer patients treated with surgical resection for whom we collected paired tissue and plasma samples. Next-generation sequencing (NGS) of all exons was performed in a targeted human comprehensive cancer panel consisting of 275 genes. RESULTS: Six patients had at least one mutation that was concordant between tissue and ctDNA sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing, 20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing identified driver mutations in 66.67% and 47.62% of the tested samples, respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and 33.33% of patients, respectively. When somatic alterations identified by each test were combined, the total proportion of patients with actionable mutations increased to 71.43%. Moreover, variants of unknown significance that were judged likely pathogenic had a higher percentage in ctDNA exclusively. Across six representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity and specificity of detection using mutations in tissue sample as a reference were 25 and 96.74%, respectively. CONCLUSIONS: This study indicates that tissue NGS and ctDNA NGS are complementary rather than exclusive approaches; these data support the idea that ctDNA is a promising tool to interrogate cancer genetics.
PURPOSE: Analysis of circulating tumor DNA (ctDNA) offers an unbiased and noninvasive way to assess the genetic profiles of tumors. This study aimed to analyze mutations in ctDNA and their correlation with tissue mutations in patients with a variety of cancers. METHODS: We included 21 cancerpatients treated with surgical resection for whom we collected paired tissue and plasma samples. Next-generation sequencing (NGS) of all exons was performed in a targeted human comprehensive cancer panel consisting of 275 genes. RESULTS: Six patients had at least one mutation that was concordant between tissue and ctDNA sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing, 20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing identified driver mutations in 66.67% and 47.62% of the tested samples, respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and 33.33% of patients, respectively. When somatic alterations identified by each test were combined, the total proportion of patients with actionable mutations increased to 71.43%. Moreover, variants of unknown significance that were judged likely pathogenic had a higher percentage in ctDNA exclusively. Across six representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity and specificity of detection using mutations in tissue sample as a reference were 25 and 96.74%, respectively. CONCLUSIONS: This study indicates that tissue NGS and ctDNA NGS are complementary rather than exclusive approaches; these data support the idea that ctDNA is a promising tool to interrogate cancer genetics.
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