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SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel
Kohei Yamashita1, Matheus Sewastjanow-Silva1, Katsuhiro Yoshimura1
1Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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.
Insights
SMARCA4 mutations are found in 7.4% of gastroesophageal adenocarcinoma patients and associate with non-signet ring cell subtype and PD-L1 positivity, but not survival. Co-occurrences with other gene mutations were also noted.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The clinical significance of SMARCA4 mutations (SMARCA4ms) in gastroesophageal adenocarcinoma (GEA) is not well understood.
- This study investigates the impact of SMARCA4ms on GEA patient outcomes.
Purpose of the Study:
- To analyze the association between SMARCA4 mutations and clinical outcomes in GEA patients.
- To identify co-occurring gene mutations with SMARCA4ms using next-generation sequencing (NGS).
Main Methods:
- Next-generation sequencing (NGS) panel profiling was performed on 256 GEA patients with metastatic or recurrent disease.
- Comparative analyses assessed clinical outcomes in relation to SMARCA4 mutation status.
- Frequencies and types of SMARCA4 mutations and their co-occurrence with other genetic alterations were examined.
Main Results:
- SMARCA4 mutations were detected in 7.4% of GEA patients.
- SMARCA4ms were significantly linked to the non-signet ring cell subtype and PD-L1 positive expression.
- No significant difference in survival was observed between patients with and without SMARCA4 mutations. Significant associations were found between SMARCA4ms and alterations in FANCA, IGF1R, KRAS, FANCL, and PTEN. Frequent co-occurrences were observed with TP53, KRAS, ARID1A, and ERBB2 mutations, primarily SNV missense types.
Conclusions:
- This study provides a comprehensive analysis of SMARCA4 mutations in GEA.
- Findings highlight the association of SMARCA4 mutations with specific GEA subtypes and PD-L1 expression, and reveal patterns of co-occurring mutations.
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