# SMARCA4‐Deficient Undifferentiated Thoracic Tumor: Clinical Features and Prognosis of a Case Series and Literature Review

## TL;DR

This paper studies a rare and aggressive lung tumor called SMARCA4-deficient undifferentiated thoracic tumor, highlighting its clinical features, poor prognosis, and potential treatment options like immunotherapy.

## Contribution

The study presents a case series and genetic analysis of SMARCA4-deficient tumors, identifying mutation hotspots and potential therapeutic approaches.

## Key findings

- SMARCA4 mutations in SNF2-related and helicase domains are linked to worse lung cancer outcomes.
- Immunotherapy and targeted therapies show partial effectiveness in treating SMARCA4-deficient tumors.
- Brain metastasis is rare in SMARCA4-deficient tumors but observed in one case.

## Abstract

Thoracic SMARCA4‐deficient undifferentiated tumors (SMARCA4‐UT) are rare and aggressive epithelioid neoplasms characterized by the loss of the SMARCA4 gene. These tumors are typically diagnosed at advanced stages and exhibit a dismal prognosis. Currently, there are no standardized treatment protocols or approved targeted therapies.

We present a case series of nine patients diagnosed of thoracic SMARCA4‐UT, detailing demographic, pathological, imaging, and treatment data. Moreover, a comprehensive literature review and genomic analysis of SMARCA4 mutations in lung cancer were also performed.

The cohort comprised predominantly male smokers (mean age: 63.0 ± 9.6 years). All cases exhibited loss of BRG1 expression, with negative staining for TTF‐1 and p40, while SMARCB1/INI‐1 expression was preserved. Patients showed poor responses to conventional chemotherapy but demonstrated partial responsiveness to immunotherapy or targeted agents. Genomic analysis of SMARCA4 mutations in lung cancer demonstrates that SMARCA4 mutations, primarily located in the SNF2‐related and helicase conserved C‐terminal domains, are associated with a poorer prognosis in lung cancer.

Immunotherapy and targeted therapies show promise in managing thoracic SMARCA4‐UT, warranting further investigation. Further exploring the genetic and molecular landscape of this tumor might reveal potential therapeutic targets.

Our manuscript presents detailed presentations of case series of thoracic SMARCA4‐UT, and we report a unique case of diaphragmatic metastases and, interestingly, the occurrence of brain metastasis in one patient, which is a rare phenomenon in SMARCA4‐UT. With a genetic analysis, it revealed that SMARCA4 mutations, primarily located within the SNF2‐related domain and the helicase conserved C‐terminal domain, are relatively common in lung cancer and are associated with a poorer prognosis.