Comparative study on the mutation spectrum of tissue DNA and blood ctDNA in patients with non-small cell lung cancer

BACKGROUND: To study the mutations detected in tissue DNA and blood circulating tumor DNA (ctDNA) of patients with advanced lung cancer and analyze the correlations between gene mutations, clinical features, and treatment. METHODS: Targeted next-generation sequencing (NGS) technology based on probe hybrid capture and Illumina high-throughput sequencing was used to detect the DNA of tumor tissue samples (n=24) and blood samples (n=15) of ctDNA from 28 lung cancer patients with a clear pathological diagnosis. For mutations, the detection range included 4 types of mutations (point mutations, small indels, copy number variations) in all exon regions and partial intron regions of the 556 genes panel. RESULTS: The most frequently detected mutant genes in 24 lung cancer tissue samples were TP53 (58.3%, 14/24), EGFR (33.3%, 8/24), LRP1B (25.0%, 6/24), KRAS (20.8%, 5/24), and ARID1A (16.7%, 4/24). The common mutant genes detected in 15 ctDNA samples were TP53 (60%, 5/15), EGFR (33.3%, 5/15), LRP1B (20.0%, 3/15), ERBB4 (3/15), and ARID1A (13.3%, 2/15). Among the 28 patients, 11 patients underwent both tissue DNA and ctDNA detection. The average co-mutation frequency of paired tissue DNA with ctDNA was 38.9% (0–83.3%), and the median value was 37.5%. CONCLUSIONS: Tissue DNA and ctDNA samples could detect genetic mutations and be consistent. Therefore, ctDNA detection as a method for disease diagnosis and evaluation of tumor molecular status may be helpful for the clinical diagnosis and treatment of lung cancer patients.