Multi-region sequencing reveals genetic correlation between esophageal squamous cell carcinoma and matched cell-free DNA.

Purpose: This study aimed to determine if both ubiquitous and heterogeneous somatic mutations could be detected in circulating cell-free DNA (cfDNA) in patients with esophageal squamous cell carcinoma (ESCC).
Methods: Paired multi-regional tumor tissues, cfDNA, and white blood cells (WBCs) were collected from five ESCC patients before treatment, as part of an ongoing prospective study (NCT02395705). Samples from Cohort 1 were sequenced by whole-exome sequencing and samples from Cohort 2 were sequenced by targeted capture sequencing. Somatic single-nucleotide variations (SNVs) were detected by comparing solid tumor or cfDNA with matched WBCs, with a minimum variant allele frequency (VAF) of 0.1% and P value <0.05.
Results: Genomic DNA (gDNA) and plasma-derived cfDNA from 26 samples were sequenced successfully. In Cohort 1, a significant linear relationship between the tumor and cfDNA VAFs (R ² = 0.78, P < 0.0001) was found. In Cohort 2, cfDNA could recover an average of 60.7% (31/51; range, 35.7-76.2%) of somatic mutations present in matched solid tumors. There was a significant positive correlation in VAFs between cfDNA and matched solid tumor tissues (R ² = 0.92, P < 0.0001).
Conclusions: Both sequencing approaches revealed high intratumoral heterogeneity in ESCC, and enabled the detection of both ubiquitous and heterogeneous mutations in cfDNA.
Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare.
(Copyright © 2021. Published by Elsevier Inc.)