Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer

Abstract

Abstract Purpose Recently developed circulating tumor DNA (ctDNA) technique is convenient and noninvasive for dynamically monitoring cancer genomic information to instruct personalized treatment. We assessed the additional value of plasma ctDNA to routine tissue next generation sequencing (NGS) of therapeutically targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC).Methods Tissue and plasma ctDNA sequencing data from 76 colorectal cancer patients were retrospectively analyzed using 556 or 105 cancer-related gene panels. The concordance of plasma-based NGS assays with solid tumor-based NGS assays was compared.Results In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). For the detection of therapeutically targetable mutations, the overall concordance of KRAS, PIK3CA, BRAF, NRAS and ERBB2 between plasma- and tissue-based analyses was 75% (57/76), 90.79% (69/76), 96.05% (73/76), 100% (76/76) and 94.74% (72/76), respectively. Moreover, the positive mutation rate of these genes by plasma plus tissue was significantly higher than that by single assay, both for individual genes and for gene combinations. Similar result was also observed for the detection of TMB-H. The increased positive mutation rate of combined tissue and plasma testing was independent of the clinical characteristics of the patients.Conclusion In conclusion, plasma ctDNA additionally increases the positive detection rate of tissue NGS only. Tissue NGS and plasma ctDNA results should be mutually complementary in clinical detection to comprehensively capture important clinically relevant genomic information for CRCs.