2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06F.04 Multi-Omics Analysis of SMARCA4-Deficient Tumors

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The study focuses on SMARCA4 (BRG1)-deficient tumors, particularly those of thoracic origin, which are known for their high malignancy and limited treatment options. A comprehensive investigation was conducted using pan-cancer surgical samples collected retrospectively between 2019 and 2023 from the National Cancer Center. These samples underwent immunohistochemistry, whole-exome sequencing, and RNA sequencing to analyze BRG1 protein deficiency, categorized into total-deficient (TD) or partial-deficient (PD) statuses, and to compare these groups to lung cancer control samples.<br /><br />Out of 66 patients assessed, most tumors originated from the lung, followed by other sites like the kidney and stomach. The study found prevalent mutations in genes such as TTN, TP53, and SMARCA4 among the TD and PD groups, with heavy smoking being a common factor. Importantly, no SMARCA4 mutations appeared in control samples, and mutations were more prevalent in the TD group compared to PD.<br /><br />In terms of DNA damage response pathways, mutations were more frequent in all deficient groups compared to controls, except for pathways like homologous recombination repair. Interestingly, certain pathways had more mutations in the PD group than in TD. Analyses also indicated that other SWI/SNF subunits like SMARCC1 had higher expression in PD than TD, suggesting potential functional compensation. High tumor mutational burden was observed in deficient groups, but with no significant differences between TD and PD.<br /><br />Additionally, the study noted that SOX-2 expression, a marker for distinguishing certain SMARCA4-deficient tumors, was highest in the TD group. This research highlights discrepancies between SMARCA4 mutations and BRG1 status, necessitating further exploration to understand varied tumor behaviors and responses to treatment.

Asset Subtitle

Yiting Dong

Meta Tag

Speaker Yiting Dong

Topic Pathology & Biomarkers

Keywords

SMARCA4-deficient tumors

thoracic origin

high malignancy

immunohistochemistry

whole-exome sequencing

RNA sequencing

BRG1 protein deficiency

tumor mutational burden

SOX-2 expression

DNA damage response pathways