Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer

Abstract

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population. Although genetic analysis of tumor tissue is often used to detect mutations in cancer genes, the invasiveness and limited accessibility hinders its application in large-scale population studies. Here, we used ultra-deep massive parallel sequencing of plasma cell free DNA (cfDNA) to identify the mutation profiles of 265 Vietnamese patients with advanced non-small cell lung cancer (NSCLC). Compared to a cohort of advanced NSCLC patients characterized by sequencing of tissue samples, cfDNA genomic testing, despite lower mutation detection rates, was able to detect major mutations in tested driver genes that reflected similar mutation composition and distribution pattern, as well as major associations between mutation prevalence and clinical features. In conclusion, ultra-deep sequencing of plasma cfDNA represents an alternative approach for population-wide genetic profiling of cancer genes where recruitment of patients is limited to the accessibility of tumor tissue site.

Keywords: actionable mutations; circulating tumor DNA; liquid biopsy; non-small cell lung cancer; targeted therapy; tissue biopsy; ultra-deep sequencing.

Figure 1

Large-scale sequencing of plasma cfDNA provides mutational profiles highly correlated to those defined by sequencing tumor tissued derived DNA in Vietnamese patients with non-small cell lung cancer. (A) Correlation analysis of driver mutation frequencies between cfDNA and ttDNA testing. (B,C) Correlated distribution of EGFR (B) and KRAS (C) mutation subtypes between cfDNA and ttDNA cohorts.