The Landscape of Actionable Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Cell-Free DNA in Chinese None Small Cell Lung Cancer

The typical tumor biopsy can be challenging to acquire in advanced or metastatic patients, and may also not capture complete genetic profiles within or across tumors. Given these limitations, a noninvasive approach, circulating cell-free DNA (cfDNA) sequence analysis shows great potential in the management of non-small cell lung cancer (NSCLC) and the prediction of drug sensitivity or resistance. Here, we drew the genetic profile using cfDNA sequence analysis in lung adenocarcinoma and squamous cell carcinoma and assess its potential clinical value. In this study, 221 tumor tissues and 174 plasma samples with NSCLC were analyzed by hybridization capture-based NGS panel including 95 cancer-associated genes. 20 significantly mutated genes were identified such as TP53, EGFR, RB1, TERT, PIK3CA, CD3EAP, CTNNB1, KIT, APC, KRAS, ERBB2, and FGFR3 et al. Among them, TP53 was the most frequently mutated gene, and had a higher mutation probability in male (p=0.0002457) or smoking (p=0.0008292) patients. 49.62% (196/395) of NSCLC patients possessed at least one actionable alteration according to the OncoKB database. Although the feasibility of genomic profiling from cfDNA was lower than that from tumor tissue DNA, the mutation landscape of target genes from cfDNA is similar to that from tumor tissue DNA, which led to a 54.05% (40/74) concordance in genomic subtyping. In summary, as an alternative for genomic profiling, cfDNA analysis is more credible in adenocarcinoma than in squamous cell carcinoma.