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While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. However, few studies have evaluated whether the frequency of multiple genomic alterations observed following ctDNA sequencing is similar to that observed following tissue sequencing in NSCLC. Therefore, in the present study, targeted next-generation sequencing (NGS) was performed on tissue and plasma ctDNA samples in 99 patients with NSCLC. Overall, the frequencies of genetic alterations detected in ctDNA were positively correlated with those detected via tissue profiling (r=0.812; P=0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor (EGFR) and tumor protein 53 (TP53; P=0.020), and between alterations in EGFR and KRAS (P=0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 (P=0.059). Furthermore, the EGFR mutant allele frequency (MAF) was positively correlated with the TP53 MAF in individual tumors (r=0.773; P=0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P=0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher compared with those in patients without ctDNA-detectable mutations. The data from the present study highlight the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of patients with NSCLC.

oncology letters

Comprehensive analysis of genomic alterations detected by next‑generation sequencing‑based tissue and circulating tumor DNA assays in Chinese patients with non‑small cell lung cancer