SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel.

Yamashita, Kohei; Sewastjanow-Silva, Matheus; Yoshimura, Katsuhiro; Rogers, Jane E; Rosa Vicentini, Ernesto; Pool Pizzi, Melissa; Fan, Yibo; Zou, Gengyi; Li, Jenny J; Blum Murphy, Mariela; Gan, Qiong; Waters, Rebecca E; Wang, Linghua; Ajani, Jaffer A

Yamashita, Kohei; Sewastjanow-Silva, Matheus; Yoshimura, Katsuhiro; Rogers, Jane E; Rosa Vicentini, Ernesto; Pool Pizzi, Melissa; Fan, Yibo; Zou, Gengyi; Li, Jenny J; Blum Murphy, Mariela; Gan, Qiong; Waters, Rebecca E; Wang, Linghua; Ajani, Jaffer A.

Afiliación

Yamashita K; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sewastjanow-Silva M; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yoshimura K; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rogers JE; Department of Pharmacy Clinical Programs, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rosa Vicentini E; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Pool Pizzi M; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Fan Y; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zou G; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Li JJ; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Blum Murphy M; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Gan Q; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Waters RE; Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wang L; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ajani JA; Departments of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cancers (Basel) ; 16(7)2024 Mar 27.

Article en En | MEDLINE | ID: mdl-38610978

ABSTRACT

ABSTRACT

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.