The Discordance of Gene Mutations between Circulating Tumor Cells and Primary/Metastatic Tumor Tissue

Abstract

Non-invasive methods are widely recommended with precision medicine. Circulating tumor cells (CTCs) are suggested to be able to solve the many limitations present in tumor tissue. As sequencing methods are being improved, studies about mutations in CTCs are burgeoning. However, major questions remain to be answered about whether the mutations in the CTCs represent the mutations in primary tumor tissue and metastatic tumor tissue and how to apply the clinical utility of the mutations in CTCs. In the searched articles, we compared the genes mutations between CTCs and tumor tissue, and extracted data about the heterogeneity of the mutational status in CTCs and the change in mutations of CTCs before and during treatment. For mutations detected in single genes, we calculated the concordance of the mutations between the CTCs and primary tumor tissue. For mutations detected in multiple genes, we calculated the concordance of the mutations between the CTCs and primary/metastatic tumor tissue. The heterogeneity of the mutational status is clear in CTCs. For mutations detected in a single gene, the total concordance of mutations is 53.05%. For mutations detected in multiple genes, the concordance of mutations is extremely high and different. Before mutations in CTCs can find widespread clinical utility, we should clarify the following subjects: amplification and sequencing errors, the definition of mutations in sequenced single CTCs, the heterogeneity of the mutational status in single CTCs, and the discordance of mutations between CTCs and tumor tissue.Therefore, the clinical application of CTCs mutations might be realized after considerably more research. Funding: This work was supported by National Institutes of Health (R21HG006173, R43HG007621, HL117929). The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This study was also funded by grants from the National Natural Science Foundation of China (81472823), the Fundamental Research Funds for Xi’an Jiaotong University (xjj2015093), the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University, China (XJTU1AHCR2014-007), and Major Basic Research Project of Natural Science of Shaanxi Provincial Science and Technology Department (2017ZDJC-11). Competing interests: The authors have declared no conflicts of interest.