18.97.9.169
18.97.9.169
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The evaluation of concordance of genomic alterations in cell-free DNA and tumor tissues via next-generation sequencing: A pilot study
( Seongmin Kim ) , ( Kyung Jin Min ) , ( Sanghoon Lee ) , ( Jin Hwa Hong ) , ( Jae Kwan Lee ) , ( Nak Woo Lee ) , ( Jae Yun Song )
UCI I410-ECN-0102-2019-500-001581515
This article is 4 pages or less.

Objective: Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a non-invasive method of assessing genomic alterations using peripheral blood. But its efficacy of clinical use in patients with ovarian cancer is not established yet. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in patients with advanced ovarian cancer. Methods: 7 patients with advanced epithelial ovarian cancers were included, The cfDNA biopsy was done just before surgery, and the tumor tissue was obtained during surgery. Both samples were analyzed by next-generation sequencing. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Results: The cfDNA amount was 107.3 in average, and showed positive correlation with advancing stage (p=0.029). Total 54 gene mutations were identified in both groups. the average number of alterations per patient for tissue and cfDNA analysis was 1.71 and 7.43, respectively. The overall concordance was 96.1% but the rate decreased to 16.6% when considering only genes with reported genomic alterations in both assays. 66.67% of mutations detected in tissue was found in cfDNA, and 16.56% of alterations detected in cfDNA was detected in tissue, indicating a potential complementary role of each assay. But the variant allele frequency (VAF) was significantly higher in concordant genes than discordant genes (p<0.001). Most frequently detected genes (TP53, BRCA1, MED12, PTCH1) showed sensitivity and specificity were 100% and 44% respectively. Conclusion: The cfDNA could detect critical mutations with high VAF in several patients. The discordancy between two samples could be explained by tumor heterogeneity, possible germline contamination of cfDNA, and difference in assay platform. The prospective studies to evaluate concordance of genomic alterations between two platforms would be necessary to determine clinical significance of cfDNA in ovarian cancer. Acknowledgements: This study was supported by Korea University Anam Hospital grant.

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