Background: The clinical impact of SMARCA4 mutations (SMARCA4ms) in gastroesophageal adenocarcinoma (GEA) remains underexplored. This study aimed to examine the association of SMARCA4ms with clinical outcomes and co-occurrence with other gene mutations identified through a next-generation sequencing (NGS) panel in GEA patients. Methods: A total of 256 patients with metastatic or recurrent GEA who underwent NGS panel profiling at the MD Anderson Cancer Center between 2016 and 2022 were included. Comparative analyses were performed to assess clinical outcomes related to SMARCA4ms. The frequency and types of SMARCA4ms and their co-occurrence with other gene mutations were also examined. Results: SMARCA4ms were identified in 19 patients (7.4%). These SMARCA4ms were significantly associated with non-signet ring cell subtype (p= 0.044) and PD-L1 positive expression (p= 0.046). No difference in survival between the SMARCA4m and SMARCA4-normal group was observed (p= 0.84). There were significant associations between SMARCA4ms and FANCA, IGF1R, KRAS, FANCL, and PTEN alterations. Notably, 15 of the 19 SMARCA4m cases involved SNV missense mutations, with frequent co-occurrences noted with TP53, KRAS, ARID1A, and ERBB2 mutations. Conclusions: These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.
背景：SMARCA4基因突变（SMARCA4ms）在胃食管腺癌（GEA）中的临床影响尚未得到充分研究。本研究旨在探讨SMARCA4ms与临床结局的关联，及其在GEA患者中通过新一代测序（NGS）检测到的其他基因突变的共现情况。方法：研究纳入了2016年至2022年间在MD安德森癌症中心接受NGS检测的256例转移性或复发性GEA患者。通过比较分析评估与SMARCA4ms相关的临床结局，并统计SMARCA4ms的发生频率、类型及其与其他基因突变的共现情况。结果：在19例患者（7.4%）中检测到SMARCA4ms。这些突变与非印戒细胞亚型（p=0.044）和PD-L1阳性表达（p=0.046）显著相关。SMARCA4突变组与正常组的生存期无显著差异（p=0.84）。SMARCA4ms与FANCA、IGF1R、KRAS、FANCL和PTEN基因改变存在显著关联。值得注意的是，19例SMARCA4突变病例中有15例为SNV错义突变，且常与TP53、KRAS、ARID1A和ERBB2突变共存。结论：本研究首次系统探讨了SMARCA4ms与GEA临床结局的关系。
肿瘤(癌症)患者之家