Comparative analysis of mutational landscapes identified from exome sequencing of tumor tissues and circulating tumor DNA

Abstract

Next-generation sequencing of circulating tumor DNA (ctDNA) has been used as a noninvasive alternative for cancer diagnosis and characterization of tumor mutational landscape. However, low ctDNA fraction and other factors can limit the ability of ctDNA analysis to capture tumor-specific and actionable variants. In this study, whole-exome sequencings (WES) were performed on paired ctDNA and tumor biopsy in 15 cancer patients to assess the extent of concordance between mutational profiles derived from the two source materials. We found that up to 16.4% ctDNA fraction can still be insufficient for detecting tumor-specific variants and that high concordance with tumor biopsy is achieved when ctDNA fraction is 30% or higher. Most importantly, ctDNA analysis can consistently capture tumor heterogeneity and detect key cancer-related genes even in a patient with both primary and metastatic tumors.