Clinical characteristics and prognostic analysis of 22 cases of SMARCA4-deficient thoracic tumors: a retrospective observational study

Introduction

SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) is a tumor suppressor gene that encodes the BRG1 protein, which is involved in chromatin remodeling, the regulation of gene expression, cell proliferation, and differentiation. SMARCA4/BRG1 (Brahma-related gene 1) deficiency leads to impaired clearance of the adenosine triphosphate (ATP)-dependent polycomb repressive complex, causing chromatin reorganization and changes in the expression levels of tumor-related genes (1,2). SMARCA4 deficiency has been observed in various tumors, including thoracic tumors, malignant rhabdoid tumors, and small cell carcinoma of the ovary, hypercalcemic type (3,4). SMARCA4-deficient thoracic tumors (SMARCA4-dTTs) exhibit two distinct histological features: rhabdoid sarcomas and epithelioid carcinomas (5).

In 2015, Le Loarer et al. first reported a SMARCA4 deficiency in thoracic tumors, which they named SMARCA4-deficient thoracic sarcoma (SMARCA4-dTS) (6). Subsequently, several reports have described the presence of SMARCA4 and BRG1 deficiencies in highly aggressive thoracic sarcomas (6-9). This type of tumor was renamed SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) in 2021, and was given a separate name in the World Health Organization (WHO) classification of thoracic tumors. SMARCA4-dTS is a rare, highly malignant thoracic tumor, with a poor prognosis (10). SMARCA4-dTTs are characterized by increased genomic instability, frequent TP53 mutations, a high tumor mutation burden, a lack of germline SMARCA4 alterations, they often expressed markers CD34 molecule (CD34), spalt-like transcription factor 4 (SALL4), and sex determining region y-box transcription factor 2 (SOX2), and have poor treatment outcomes with patients often dying within a few months (6,9).

In recent years, SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) has been recognized as a unique subtype of SMARCA4-dTTs that is also rare and highly malignant (11). The incidence of SMARCA4/BRG1 deficiency in NSCLC lines is 33% (12), while in other tumor specimens, it ranges from 3% to 15% (13,14). Currently, limited descriptions of the pathological features are available. Tumor tissues are usually negative for thyroid transcription factor-1 (TTF-1), and tumor protein 40 (P40), and positive for cytokeratin 7 (CK7) and Hep-par-1 (11). The responses of SMARCA4-dNSCLC to immunotherapy and chemotherapy vary, and the prognosis is inconsistent (15,16). Currently, there is no clear standard treatment regimen for SMARCA4-dTTs. The efficacy of platinum-based chemotherapy, targeted therapy, and immunotherapy in these tumors is limited (17,18). Therefore, more exploration and research are needed for this type of tumor.

Our study provides a detailed description of 22 cases of SMARCA4-dTTs, including SMARCA4-dUT and SMARCA4-dNSCLC, including the clinical characteristics, pathological morphological features, imaging features, treatment regimens, and prognosis. Combined with a literature review, we analyze and discuss the diagnosis, treatment methods, and prognosis of SMARCA4-dTTs to provide a clinical basis for the diagnosis and treatment of SMARCA4-dTTs in the future. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-2002/rc).

Methods

Study population

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective observational clinical study was approved by Xijing Hospital’s ethics committee (ethics approval No. KY20252097-F-1) and informed consent was taken from the patients’ family. We enrolled 2,566 patients with pulmonary tumors who attended Xijing Hospital from January 2022 to June 2024, and screened out 22 inpatients with SMARCA4-dTTs as confirmed by immunohistochemical staining (Figure 1). We collected the clinical data of the patients, including gender, age, smoking status, main symptoms, family history of tumors, Eastern Cooperative Oncology Group performance status (ECOG-PS) score, programmed cell death ligand 1 (PD-L1) TPS (<1%, 1–49%, ≥50%), distant metastasis status at diagnosis and any time after initial diagnosis, treatment regimens, and survival status. Patients were followed up for at least 6 months or until death.

Figure 1 Flowchart showing patient inclusion and exclusion criteria. IHC, immunohistochemistry.

Diagnostic criteria

All patients were diagnosed according to the WHO Classification of Thoracic Tumors (5th edition), and staged according to the Tumor-Node-Metastasis (TNM) Staging System for Lung Cancer (8th edition). The final diagnosis and staging were based on the biological and clinical characteristics of the tumor, including imaging, pathological, and molecular features. The pathological features and diagnosis were confirmed by two pathologists with over 10 years of experience each. The imaging features and TNM staging were confirmed by two thoracic oncology specialists with over 10 years of experience each, based on the TNM Staging System for Lung Cancer (8th edition).

Statistical analysis

The normally distributed continuous data are presented as the mean ± standard deviation, the non-normally distributed data as the median (interquartile range), and the categorical data as the percentage. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to compare survival differences between groups. Overall survival (OS) was defined as the time from the start of treatment to death; if a patient was still alive during the follow-up period, the survival time was censored. The data analysis was performed using SPSS 25.0 software (SPSS Inc., IBM Corp., Chicago, USA). A P value <0.05 was considered statistically significant.

Results

Clinical characteristics of 22 patients with SMARCA4-dTTs

This study analyzed the clinical characteristics of 22 patients with SMARCA4-dTTs (Table 1). Most of the SMARCA4-dTTs patients were male (95.5%, 21/22) and smokers (90.9%, 20/22), with hilar lymph node metastasis (4/22), mediastinal lymph node metastasis (18/22), and distant metastasis (15/22) (Table 1 and Figure 2). Only one patient had a positive driver gene mutation [1/22, rearranged during transfection (RET) fusion].

Figure 2 Chest CT imaging manifestations of eight typical patients. (A1-H1) Represents the lung window manifestations of the patients’ chest CT; (A2-H2) represents the mediastinal window manifestations, and the yellow arrows indicate the tumor lesions. CT, computed tomography.

Imaging characteristics of SMARCA4-dTTs

The thoracic imaging manifestations of 22 patients with SMARCA4-dTTs are shown in Table 2, and typical computed tomography (CT) findings in selected patients are illustrated in Figure 2. Based on tumor location, 15 patients (68.2%) had central-type tumors, while seven (31.8%) had peripheral-type tumors. The median tumor length was 4.85 cm (range, 3.4–6.58 cm), and the median tumor width was 3.5 cm (range, 2.4–5.0 cm). Twelve patients (54.5%) had spiculation, 18 (81.8%) had lobulation, and six (27.3%) had pleural indentation. Eight patients (36.4%) had atelectasis, six (27.3%) had obstructive pneumonia, and three (13.6%) had pleural effusion. All patients (100%) had enlarged lymph nodes.

Pathological results of SMARCA4-dTTs

Immunohistochemical staining of the 22 SMARCA4-dTTs showed SMARCA4 deficiency (Figures 3,4), with no integrase interactor 1 (INI-1) deficiency and high Ki-67 expression (NSCLC, >20% is considered high expression), with values of 67.3%±17.4% and 82.1%±15.5% (Table 1). Fifteen patients were diagnosed with SMARCA4-dNSCLC. Histologically, the tumor tissue appeared in nests and cords under low magnification, with some glandular structures. Under high magnification, the tumor cells had pleomorphic nuclei with irregular shapes and frequent mitotic figures. The epithelial markers cytokeratin (CK) (AE1/AE3) and CK7 were positive, while other common NSCLC markers such as TTF-1, Napsin A, p40, and neuroendocrine markers such as synaptophysin (syn) were negative (Figure 3). Seven patients were diagnosed with SMARCA4-dUTs. Under low magnification, the tumor cells were spindle-shaped and disorganized. Under high magnification, the tumor cells exhibited significant atypia with irregular nuclei and frequent nuclear fragmentation. There was no evidence of epithelial differentiation, with CK (AE1/AE3), CK5/6, TTF-1, Napsin A, p40, and Claudin-4 all being negative (Figure 4).

Figure 3 Pathological results of SMARCA4-dNSCLC. The first and second images show the results of hematoxylin and eosin staining of lymph node biopsy tissue, magnifications: ×20 (first image), and ×40 (second image). The remaining images are typical biomarkers of lung tumor by IHC staining; the signs (+)/(−) on the upper corners indicate positive or negative results according to the IHC staining. Magnification: ×40. CK, cytokeratin; dNSCLC, deficient non-small cell lung cancer; IHC, immunohistochemistry; P40, protein 40; TTF-1, thyroid transcription factor-1.

Figure 4 Pathological results of SMARCA4-dUTs. The first and second images show the results of hematoxylin and eosin staining of lymph node biopsy tissue; magnifications: ×20 (first image), and ×40 (second image). The remaining images are typical biomarkers of lung tumor by IHC staining; the signs (+)/(−) on the upper corners indicate positive or negative results according to the IHC staining. Magnification: ×40. CK, cytokeratin; dUT, deficient undifferentiated tumor; IHC, immunohistochemistry; P40, protein 40; PD-L1, programmed cell death ligand 1; TTF-1, thyroid transcription factor-1.

Treatment and survival of SMARCA4-dTTs

The median OS of the 22 patients was 4 months. Three patients (Nos. 1/3/6) did not receive anti-tumor treatment due to financial constraints, two (Nos. 2/5) did not receive treatment due to high ECOG-PS scores, and one (No. 4) refused treatment due to advanced age. Two patients with early-stage disease underwent surgery combined with adjuvant chemotherapy and had longer survival times, with their current OS reaching 22 months and 12 months, respectively. The remaining 14 patients received various treatments based on TNM staging and their individual conditions, including chemotherapy alone, chemotherapy combined with immunotherapy, chemotherapy combined with anlotinib, chemotherapy combined with radiotherapy, palliative radiotherapy, and oral anlotinib therapy (Figures 5,6). One patient with RET fusion received targeted therapy (pralsetinib) after first-line chemotherapy failure for 6 months (Figure 3). Based on tumor staging (median OS, non-stage IV patients 12 months, stage IV patients 3 months, P<0.01), the untreated and treated patients had median survival times of 1 month and 7 months, respectively, with a statistically significant difference (P<0.01). Among the treated patients, no survival differences were observed in terms of whether or not they received immunotherapy, anlotinib, or radiotherapy (P>0.05) (Figure 7).

Figure 5 Pathological and baseline metastasis of 22 patients with SMARCA4-dTTs, N1: metastasis of lymph nodes around the ipsilateral bronchus and/or hilar lymph nodes, and lymph nodes in the ipsilateral lung, N2: metastasis of mediastinal lymph nodes and/or subcarinal lymph nodes on the ipsilateral side; N3: metastasis to the contralateral mediastinum, contralateral hilum, ipsilateral, or contralateral anterior scalene muscle, and supraclavicular lymph nodes. dNSCLC, deficient non-small cell lung cancer; dTT, deficient thoracic tumor; dUT, deficient undifferentiated tumor.

Figure 6 Treatment regimens and survival times of 22 patients with SMARCA4-dTTs. In Figure 5, the order of the patients is the same as in this figure, i.e., in ascending order of total survival (patient No. 1–22). dTT, deficient thoracic tumor.

Figure 7 Survival analysis of 22 patients with SMARCA4-dTTs. dNSCLC, deficient non-small cell lung cancer; dTT, deficient thoracic tumor; dUT, deficient undifferentiated tumor.

Discussion

SMARCA4-dTTs are a rare and highly malignant group of tumors, characterized by the loss or mutation of the SMARCA4 gene, leading to the absence of BRG1 protein expression. BRG1, as a core subunit of the SWI/SNF chromatin remodeling complex, is involved in key cellular functions such as gene expression regulation, cell proliferation, and differentiation (19). SMARCA4 deficiency leads to an abnormal chromatin structure, which in turn promotes tumor occurrence and progression (6).

This study retrospectively investigated the clinical manifestations, thoracic imaging, pathological features, survival, and prognosis of 22 patients with confirmed SMARCA4-dTTs. Consistent with previous report (20), we first observed that SMARCA4-dTTs predominantly occur in male smokers. The high incidence of SMARCA4 deficiency in smokers may be related to increased genomic instability (12). Most patients presented with various intra- and extra-thoracic symptoms at the time of diagnosis, indicating that these tumors are often in advanced or locally advanced stages, reflecting the high invasiveness and rapid metastatic potential of this type of thoracic tumor (21,22). This further highlights the importance of early screening and diagnosis for thoracic tumors.

The imaging manifestations of SMARCA4-dTTs are diverse. Thoracoabdominal CT may show large pulmonary masses compressing the pulmonary artery, mediastinal masses, enlarged hilar and mediastinal lymph nodes, multiple enlarged lymph nodes in the peritoneum and retroperitoneum compressing the superior vena cava and brachiocephalic vein (23,24), as well as pleural and pericardial effusions (25), which are consistent with the findings in this study. SMARCA4-dTTs mostly present as central-type pulmonary masses with mediastinal lymphadenopathy. Therefore, in clinical screening, if similar imaging manifestations are observed, this rare type of tumor should be considered to avoid misdiagnosis.

The key to diagnosing SMARCA4-dTTs is the detection of SMARCA4 protein expression loss by immunohistochemistry (IHC). Most typical cases show a complete absence of SMARCA4 (BRG1) expression, while about 25% of cases show diffuse weakening of SMARCA4 staining (6). In this study, all 22 patients’ pathological tissues showed SMARCA4 deficiency. Additionally, SMARCA2 is often co-deleted, while SMARCB1 expression is retained (6). Moreover, these tumors usually do not express or only focally express epithelial markers [e.g., CK and epithelial membrane antigen (EMA)], while markers such as Claudin-4, p63, and TTF-1 are mostly negative (6,26,27). There are also cases with positive TTF-1 (28). These are the key markers for differentiating between SMARCA4-dNSCLC (epithelial marker CK positive) and SMARCA4-dUTs.

Difficulties have arisen in the pathological diagnosis of SMARCA4-dTTs, with diagnoses including poorly differentiated carcinoma and thoracic sarcoma. In this study, four cases were initially reported as poorly differentiated carcinoma, and three as SMARCA4-dTS. After discussion with pathologists and additional immunohistochemical staining, the diagnoses were changed to the standardized SMARCA4-dNSCLC and SMARCA4-dUT. Additionally, all patients had high Ki-67 expression, indicating high tumor malignancy. Molecular pathology techniques such as Sanger sequencing, fluorescence in situ hybridization, and next-generation sequencing can also be used for diagnosis and differential diagnosis (6,8,27), but they are expensive and not readily available, and thus are not the first choice in clinical practice compared to IHC.

SMARCA4-dTTs have a poor prognosis and lack a standard treatment regimen (29). Treatment strategies mainly include surgery, chemotherapy, radiotherapy, immunotherapy, and emerging targeted therapies. Surgery is the preferred treatment for early-stage or locally advanced SMARCA4-dTTs, but due to the tumors’ local invasiveness and tendency for distant metastasis, surgical opportunities are limited. For resectable tumors, some patients who underwent surgery combined with adjuvant chemotherapy (even with bevacizumab) had a survival extension of up to 20 months (6). For example, one of our patients (No. 22) had a progression-free survival (PFS) time of 18 months after surgery combined with adjuvant therapy and is still under follow-up. However, there is also a report of patients who died within 4 months of surgery without adjuvant treatment (30). Therefore, for operable patients, radical surgery combined with adjuvant therapy may be an effective treatment strategy.

For most inoperable patients, chemotherapy and radiotherapy are the main treatment modalities. SMARCA4-dTTs generally have a poor response to chemotherapy (10), with survival not usually exceeding 9 months (6). Indeed, most patients survive less than 6 months or even less than 1 month after one or more chemotherapy regimens (4,27,31). However, chemotherapy in combination with radiotherapy may improve patient prognosis, with some patients surviving more than 12 months (6). For example, in our study, two patients (Nos. 9 and 10) had a survival of only 3–4 months after chemotherapy, but another patient (No. 16) had an extended survival of 8 months after chemotherapy combined with radiotherapy. Although there was no statistical difference in whether radiotherapy was combined (Figure 7), there was still a benefit for individual patients.

In recent years, immunotherapy and anti-angiogenic therapy have shown some potential in the treatment of SMARCA4-dTTs (15,24,32). Some patients have received monotherapy with immune checkpoint inhibitors, as well as combinations of immune checkpoint inhibitors with chemotherapy or anti-angiogenic drugs. For example, Takada et al. reported that a patient with 60% PD-L1 expression had a total survival time of 26 months after treatment with pembrolizumab (24). Kawachi et al. reported that, regardless of PD-L1 expression levels, patients treated with a combination of atezolizumab, bevacizumab, paclitaxel, and carboplatin showed strong therapeutic effects, with PFS of up to 17 months in some cases (33). Anžič et al. reported that a patient who was initially treated with pembrolizumab, then ipilimumab after disease progression, followed by carboplatin and paclitaxel, palliative radiotherapy, doxorubicin, and cyclophosphamide, had a total survival time of 25 months (23). Additionally, some patients treated with iodine-125 seed implantation combined with camrelizumab, liposomal paclitaxel, and nedaplatin were reported to have PFS of over 19 months (34). Overall, no specific drug has yet been shown to have an advantage in the treatment of SMARCA4-dTTs.

Although the detection rate of driver genes in SMARCA4-dTTs is low, some novel targeted therapies are emerging. For example, CDK4/6 inhibitors have shown good efficacy in SMARCA4-deficient tumors (35). EZH2 inhibitors also have significant potential in SMARCA4-dTTs, inducing cell cycle arrest and apoptosis, and inhibiting tumor growth and metastasis (29). Tazemetostat, a selective EZH2 inhibitor, has demonstrated antitumor effects in various SMARCA4-deficient tumor models (36,37). A phase I/II clinical trial targeting pediatric INI/SMARCA4 protein-deficient solid tumors is currently recruiting, mainly to evaluate the efficacy of tazemetostat in combination with nivolumab and ipilimumab (NCT05407441). Some studies have found that SMARCA4-deficient tumors may be sensitive to certain targeted therapies, such as ATR inhibitors and KDM6 inhibitors (38-40), which also provide new directions for future targeted therapies. However, most of these studies are in the early stages, and more clinical trials are required to verify the efficacy and safety of these treatments.

This study had some limitations. Since SMARCA4-dTTs are rare, the number of cases confirmed at Xijing Hospital was small, and the sample size of the study was limited. Additionally, there is currently no standard treatment for this type of tumor, resulting in diverse and non-uniform treatment regimens in our study. However, the results of this study indicate that early detection and active use of multiple treatment modalities may be key to improving survival in this type of tumor.

Conclusions

SMARCA4-dTTs are a group of highly malignant, highly invasive tumors with a poor prognosis. Since they were first reported in 2015, thoracic oncologists have gradually gained a deeper understanding of these tumors. This study suggests that SMARCA4-related testing should be performed for patients with thoracic tumors with central-type masses and mediastinal lymph node metastasis on imaging, and low-differentiated morphology to avoid missed diagnoses and to formulate appropriate further diagnostic and treatment strategies. Although there is no standard treatment, early detection and active treatment can result in some survival benefits.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-2002/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-2002/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-2002/prf

Funding: This study was supported by the National Natural Science Foundation of China (No. 81601989) and Key Research and Development Program of Shaanxi (No. 2019SF-097).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-2002/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective observational clinical study was approved by Xijing Hospital’s ethics committee (ethics approval No. KY20252097-F-1) and informed consent was taken from the patients’ family.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Biegel JA, Busse TM, Weissman BE. SWI/SNF chromatin remodeling complexes and cancer. Am J Med Genet C Semin Med Genet 2014;166C:350-66. [Crossref] [PubMed]
2. Nambirajan A, Singh V, Bhardwaj N, et al. SMARCA4/BRG1-Deficient Non-Small Cell Lung Carcinomas: A Case Series and Review of the Literature. Arch Pathol Lab Med 2021;145:90-8. [Crossref] [PubMed]
3. Errichiello E, Mustafa N, Vetro A, et al. SMARCA4 inactivating mutations cause concomitant Coffin-Siris syndrome, microphthalmia and small-cell carcinoma of the ovary hypercalcaemic type. J Pathol 2017;243:9-15. [Crossref] [PubMed]
4. Sauter JL, Graham RP, Larsen BT, et al. SMARCA4-deficient thoracic sarcoma: a distinctive clinicopathological entity with undifferentiated rhabdoid morphology and aggressive behavior. Mod Pathol 2017;30:1422-32. [Crossref] [PubMed]
5. Decroix E, Leroy K, Wislez M, et al. SMARCA4-deficient thoracic tumors: A new entity. Bull Cancer 2020;107:41-7. [Crossref] [PubMed]
6. Le Loarer F, Watson S, Pierron G, et al. SMARCA4 inactivation defines a group of undifferentiated thoracic malignancies transcriptionally related to BAF-deficient sarcomas. Nat Genet 2015;47:1200-5. [Crossref] [PubMed]
7. Iijima Y, Sakakibara R, Ishizuka M, et al. Notable response to nivolumab during the treatment of SMARCA4-deficient thoracic sarcoma: a case report. Immunotherapy 2020;12:563-9. [Crossref] [PubMed]
8. Rekhtman N, Montecalvo J, Chang JC, et al. SMARCA4-Deficient Thoracic Sarcomatoid Tumors Represent Primarily Smoking-Related Undifferentiated Carcinomas Rather Than Primary Thoracic Sarcomas. J Thorac Oncol 2020;15:231-47. [Crossref] [PubMed]
9. Perret R, Chalabreysse L, Watson S, et al. SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses. Am J Surg Pathol 2019;43:455-65. [Crossref] [PubMed]
10. Nicholson AG, Tsao MS, Beasley MB, et al. The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol 2022;17:362-87. [Crossref] [PubMed]
11. Agaimy A, Fuchs F, Moskalev EA, et al. SMARCA4-deficient pulmonary adenocarcinoma: clinicopathological, immunohistochemical, and molecular characteristics of a novel aggressive neoplasm with a consistent TTF1(neg)/CK7(pos)/HepPar-1(pos) immunophenotype. Virchows Arch 2017;471:599-609. [Crossref] [PubMed]
12. Matsubara D, Kishaba Y, Ishikawa S, et al. Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features. Cancer Sci 2013;104:266-73. [Crossref] [PubMed]
13. Herpel E, Rieker RJ, Dienemann H, et al. SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: immunohistochemical survey of 316 consecutive specimens. Ann Diagn Pathol 2017;26:47-51. [Crossref] [PubMed]
14. La Fleur L, Falk-Sörqvist E, Smeds P, et al. Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11. Lung Cancer 2019;130:50-8. [Crossref] [PubMed]
15. Naito T, Umemura S, Nakamura H, et al. Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: A case report. Thorac Cancer 2019;10:1285-8. [Crossref] [PubMed]
16. Tagal V, Wei S, Zhang W, et al. SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers. Nat Commun 2017;8:14098. [Crossref] [PubMed]
17. Dagogo-Jack I, Schrock AB, Kem M, et al. Clinicopathologic Characteristics of BRG1-Deficient NSCLC. J Thorac Oncol 2020;15:766-76. [Crossref] [PubMed]
18. Schoenfeld AJ, Bandlamudi C, Lavery JA, et al. The Genomic Landscape of SMARCA4 Alterations and Associations with Outcomes in Patients with Lung Cancer. Clin Cancer Res 2020;26:5701-8. [Crossref] [PubMed]
19. Bögershausen N, Wollnik B. Mutational Landscapes and Phenotypic Spectrum of SWI/SNF-Related Intellectual Disability Disorders. Front Mol Neurosci 2018;11:252. [Crossref] [PubMed]
20. Utsumi T, Taniguchi Y, Noda Y, et al. SMARCA4-deficient undifferentiated tumor that responded to chemotherapy in combination with immune checkpoint inhibitors: A case report. Thorac Cancer 2022;13:2264-6. [Crossref] [PubMed]
21. Mundada M, Mannan KA, Vasu D, et al. Under the Microscope: A Case Report of Thoracic SMARCA4-Deficient Undifferentiated Tumor with Review of the Literature. Turk Patoloji Derg 2024;40:128-33. [Crossref] [PubMed]
22. Yin C, Liu ZJ, He C, et al. A case of surgically treated non-metastatic SMARCA4-deficient undifferentiated thoracic tumor: a case report and literature review. Front Oncol 2024;14:1399868. [Crossref] [PubMed]
23. Anžič N, Krasniqi F, Eberhardt AL, et al. Ipilimumab and Pembrolizumab Mixed Response in a 41-Year-Old Patient with SMARCA4-Deficient Thoracic Sarcoma: An Interdisciplinary Case Study. Case Rep Oncol 2021;14:706-15. [Crossref] [PubMed]
24. Takada K, Sugita S, Murase K, et al. Exceptionally rapid response to pembrolizumab in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1: A case report. Thorac Cancer 2019;10:2312-5. [Crossref] [PubMed]
25. Shi L, Lin L, Ding Y, et al. Case report: A rapid response to immunotherapy in a thoracic SMARCA4-deficient undifferentiated tumor with respiratory failure. Front Oncol 2022;12:1020875. [Crossref] [PubMed]
26. Kunimasa K, Okami J, Takenaka S, et al. Conversion Surgery for Advanced Thoracic SMARCA4-Deficient Undifferentiated Tumor With Atezolizumab in Combination With Bevacizumab, Paclitaxel, and Carboplatin Treatment: A Case Report. JTO Clin Res Rep 2021;2:100235. [Crossref] [PubMed]
27. Yoshida A, Kobayashi E, Kubo T, et al. Clinicopathological and molecular characterization of SMARCA4-deficient thoracic sarcomas with comparison to potentially related entities. Mod Pathol 2017;30:797-809. [Crossref] [PubMed]
28. Mehta A, Diwan H, Bansal D, et al. TTF1-positive SMARCA4/BRG1 deficient lung adenocarcinoma. J Pathol Transl Med 2022;56:53-6. [Crossref] [PubMed]
29. Li X, Tian S, Shi H, et al. The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation. Cancer Gene Ther 2024;31:687-97. [Crossref] [PubMed]
30. Iguchi T, Mizuguchi S, Chung K, et al. A dramatic course after the resection of an SMARCA4-deficient undifferentiated tumour. Respirol Case Rep 2022;10:e01001. [Crossref] [PubMed]
31. Crombé A, Alberti N, Villard N, et al. Imaging features of SMARCA4-deficient thoracic sarcomas: a multi-centric study of 21 patients. Eur Radiol 2019;29:4730-41. [Crossref] [PubMed]
32. Henon C, Blay JY, Massard C, et al. Long lasting major response to pembrolizumab in a thoracic malignant rhabdoid-like SMARCA4-deficient tumor. Ann Oncol 2019;30:1401-3. [Crossref] [PubMed]
33. Kawachi H, Kunimasa K, Kukita Y, et al. Atezolizumab with bevacizumab, paclitaxel and carboplatin was effective for patients with SMARCA4-deficient thoracic sarcoma. Immunotherapy 2021;13:799-806. [Crossref] [PubMed]
34. Li B, Li XG. Iodine-125 Seed Implantation and Transarterial Chemoinfusion Combined with Immune Checkpoint Inhibitors for a Thoracic SMARCA4-Deficient Undifferentiated Tumor. J Vasc Interv Radiol 2023;34:147-9. [Crossref] [PubMed]
35. Lee EK, Esselen KM, Kolin DL, et al. Combined CDK4/6 and PD-1 Inhibition in Refractory SMARCA4-Deficient Small-Cell Carcinoma of the Ovary, Hypercalcemic Type. JCO Precis Oncol 2020;4:736-42. [Crossref] [PubMed]
36. Simeone N, Frezza AM, Zaffaroni N, et al. Tazemetostat for advanced epithelioid sarcoma: current status and future perspectives. Future Oncol 2021;17:1253-63. [Crossref] [PubMed]
37. Yuan H, Nishikori M, Otsuka Y, et al. The EZH2 inhibitor tazemetostat upregulates the expression of CCL17/TARC in B-cell lymphoma and enhances T-cell recruitment. Cancer Sci 2021;112:4604-16. [Crossref] [PubMed]
38. Kurashima K, Kashiwagi H, Shimomura I, et al. SMARCA4 deficiency-associated heterochromatin induces intrinsic DNA replication stress and susceptibility to ATR inhibition in lung adenocarcinoma. NAR Cancer 2020;2:zcaa005. [Crossref] [PubMed]
39. Romero OA, Vilarrubi A, Alburquerque-Bejar JJ, et al. SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade. Nat Commun 2021;12:4319. [Crossref] [PubMed]
40. Xue Y, Meehan B, Macdonald E, et al. CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary. Nat Commun 2019;10:558. [Crossref] [PubMed]

(English Language Editor: L. Huleatt)