The genomic landscape of SMARCA4 and the clinical characteristics in Chinese NSCLC patients.

Abstract

e21010 Background: The tumor suppressor gene SMARCA4 encodes a submit of SWI/SNF chromatin remodeling complexes and inactivated by mutations or other mechanisms. Previous studies have reported the genomic landscape of SMARCA4 and the clinical impact in Caucasian population, but the molecular and clinical characteristics in Chinese NSCLC patients have never reported. Herein, we explore the SMARCA4 profiles in Chinese population. Methods: A total of 740 patients of NSCLC with paired tumor-normal samples were collected into the study, all samples were detected by DNA based sequencing with a 1021 gene panel. Results: The incidence of SMARCA4 mutation in Chinese NSCLC patients was 7.16% (53/740), the top10 co-mutated genes were TP53, LRP1B, KEAP1, EGFR, KRAS, HGF, FGFR1, FAT1, CDKN2A, STK11. The SMARCA4 alterations were divided to functional or unfunctional mutations according to the OncoKB database (developed by MSKCC), then we compared the clinical characteristics among the SMARCA4-functional (S-F), SMARCA4-unfunctional (S-UNF) and SMARCA4-wide type (S-WT) patients. The results showed the S-F group tended to have more Male patients (88% vs. 64% vs. 55%, p = 0.004) and more smokers (68% vs. 46% vs. 34%, p = 0.015), meanwhile the age and histopathological subtype showed no significant difference among the three groups. We also analyzed the mutation burden characteristics, The S-F group have more somatic mutations (19.20 vs. 16.29 vs. 9.06, p < 0.0001) and higher TMB value (15.67 vs. 12.20 vs.5.61, p < 0.0001), indicating the patients may have more clinical benefits from immunotherapy. As recent studies revealed the SMARCA4 alterations associated with a very poor prognosis in NSCLC, according to our results, the immunotherapy may be an alternative strategy, and this need more clinical explorations. Conclusions: The patients with SMARCA4-functional mutations were associated with Male and smoker in Chinese population and tended to have more somatic mutations and higher TMB value, thus may benefit more from immunotherapy.