Clinicopathological and molecular features of lung carcinomas with abnormal SMARCA2 expression and preserved...

The clinicopathological significance and molecular basis of abnormal SMARCA2 expression in lung carcinoma remain poorly understood. We retrospectively analyzed 16 poorly differentiated lung carcinomas showing complete loss or diffuse marked reduction of SMARCA2 expression with preserved SMARCA4 and SMARCB1. The tumors exhibited a broad morphological spectrum and were classified as adenocarcinoma (n = 10), non-small cell carcinoma favoring adenocarcinoma (n = 2), squamous cell carcinoma (n = 3), or non-small cell carcinoma, not otherwise specified (n = 1). Clinical molecular testing revealed diverse molecular alterations, including KRAS, EGFR, ALK, TP53, PIK3CA, and CD274 abnormalities. Targeted SMARCA2 sequencing, performed in 11 cases, identified pathogenic or likely pathogenic alterations in four tumors without recurrent hotspot mutations. DNA methylation analysis of two CpG-rich regions, performed in nine cases, did not identify a consistent hypermethylation pattern within the analyzed regions. These findings demonstrate considerable morphological and molecular heterogeneity among lung carcinomas with abnormal SMARCA2 expression and preserved SMARCA4/SMARCB1. Recurrent SMARCA2 hotspot mutations and consistent hypermethylation of the analyzed CpG-rich regions were not identified, indicating that additional mechanisms may contribute to abnormal SMARCA2 expression.