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Identification of tumor-derived mutation (TDM) in liquid biopsies (LB), especially in early-stage patients, faces several challenges, including low variant-allele frequencies, interference by white blood cell (WBC)-derived mutations (WDM), benign somatic mutations and tumor heterogeneity. Here, we addressed the above-mentioned challenges in a cohort of 50 nonmetastatic colorectal cancer patients, via a workflow involving parallel sequencing of paired WBC- and tumor-gDNA. After excluding potential false positive mutations, we detected at least one TDM in LB of 56% (28/50) of patients, with the majority showing low-patient coverage, except for one TDM mapped to  KMT2D  that recurred in 30% (15/30) of patients.

Ultra-Deep Sequencing of Plasma-Circulating DNA for the Detection of Tumor- Derived Mutations in Patients with Nonmetastatic Colorectal Cancer