We present a treatment-naïve SMARCA4-DNSCLC case with synchronous brain metastasis harboring a unique genomic profile: concurrent mutations in chromatin remodeling genes (SMARCA4, CHD8, NSD1) and DDR pathway genes (ATR, BARD1, TP53), accompanied by elevated tumor mutational burden (TMB-H). The gene discussed is TP53; the disease is neoplasm.