Next‑generation sequencing elucidates the distinct mutational landscape of SMARCA4‑deficient lung cancer

Lung cancer with SMARCA4 deficiency has a high degree of malignancy and a low degree of differentiation. It is a newly discovered type of tumor closely related to gene mutations. The present study aimed to clarify the molecular mutation characteristics of SMARCA4‑deficient lung cancer using next‑generation sequencing (NGS). NGS sequencing was conducted to analyze the gene expression profile of 15 patients with SMARCA4‑deficient lung cancer, with positive or negative EGFR expression, and the association between gene mutation sites and SMARCA4 expression was analyzed. The pathological characteristics of SMARCA4‑deficient lung cancer were analyzed using immunohistochemistry. The likelihood of positivity for the programmed cell death 1 ligand 1 protein was low, and there were no instances of positivity for anaplastic lymphoma kinase protein expression. Approximately 50% of Ki67‑positive expression regions were present. The BOI‑related E3 ubiquitin‑protein ligase 1 protein encoded by the SMARCA4 gene was not expressed; however, the INI1 protein encoded by SMARCB1 was partially positive (6/15), which showed that the expression of INI1 was not affected by SMARCA4. The SMARCA4 mutation types included c.2729C>T (p.T910M), c.3634_3636del (p.E1212del), c.3574C>T (p.R1192C), and c.3733G>A (p.A1245T). NQO1 and TP53 mutations were detected in nine patients, XRCC1 mutation was detected in seven patients, DPYD mutation was detected in six patients and TYMS mutation was detected in five patients. The mutated genes were more resistant to the EGFR tyrosine kinase inhibitor. In conclusion, patients with SMARCA4‑deficient lung cancer have distinct immunohistochemical characteristics, and SMARCA4 has been implicated in the incidence and progression of tumors through different mutation mechanisms.