Concurrent somatic alterations of TP53 and RB1 in Chinese lung adenocarcinoma with or without EGFR mutations.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21526-e21526
Author(s):  
JUN WANG ◽  
Gang Chen ◽  
Bicheng Zhang ◽  
Jianguo Sun ◽  
Jing Liang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Wild Type ◽  
Mutational Status ◽  
Significant Difference ◽  
Somatic Alterations ◽  
Egfr Mutant ◽  
Mutant Egfr

e21526 Background: Endothelial growth factor receptor (EGFR)-mutant lung adenocarcinoma displays diverse responses to tyrosine kinase inhibitor therapy. Concurrent somatic alterations represent different biological substantial proportion of patients with EGFR mutations and impacts their prognosis. Methods: We conducted this retrospective study to clarify the comprehensive concurrent genetic alterations of TP53 and RB1 and tumor mutational burden (TMB) in 712 EGFR-mutant or EGFR-wild type lung adenocarcinoma by next generation sequencing-based gene panel tests. Results: EGFR was the most frequently mutated gene altered in 58.0% (413/712) of lung adenocarcinoma, followed by TP53 altered in 56.7%, KRAS altered in 13.3%, and RBM10 altered in 11.2% of all patients. Concurrent genetic alteration of TP53 and RB1 is more likely to be found in EGFR-mutant patients than in EGFR-wild type patients, with a frequency of 11.4% (45/413) and 4.3% (13/299), respectively (p = 0.003). However, the frequency of TP53 and RB1 concurrent alteration was similar in lung cancer with sensitive EGFR mutation compared to those with non-sensitive mutation (10.5% versus 11.6%). TP53 mutation was most frequently found in patients with RB1 mutation (58/61), irrespective of EGFR mutational status. Furthermore, significant difference was found regarding median TMB in patients with mutant EGFR compared to those with non-mutant EGFR (3.8 versus 4.3; p < 0.001). Median TMB was higher for patients with TP53 and RB1 concurrent alteration than those without concurrent alteration in all patients (5.4 versus 4.3, p = 0.018). Conclusions: Our data showed that high prevalence of concurrent somatic alterations of TP53 and RB1 genes among lung adenocarcinoma patients with EGFR mutations, which might help understand several key biological processes and develop potential therapeutic strategies.

Investigation of immune microenvironment in EGFR mutant NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20517-e20517
Author(s):  
Yi Hu ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Yuezong Bai ◽  
Fan Zhang
Keyword(s):  
T Cells ◽  
Egfr Mutation ◽  
Tumor Stroma ◽  
Median Number ◽  
Egfr Mutations ◽  
Wild Type ◽  
Immune Microenvironment ◽  
Regulatory Pathways ◽  
Significant Difference ◽  
Egfr Mutant

e20517 Background: Immune checkpoint inhibitor therapy has made great achievements in NSCLC, but patients with EGFR mutations have poor efficacy with immunotherapy. Previous studies have explored the expression of PD-L1, neo-antigen, co-mutation and regulatory pathways in EGFR mutate NSCLC. This work compared the immune microenvironment of EGFR mutant and wild-type NSCLC. Methods: Patients: NSCLC. Using multi-color immunohistochemistry (multi-IHC) to evaluate the expression of 2 indicators in tumors and tumor stroma, namely CD8+ T cell and macrophage. Shapiro-Wilk was used for normality test, and t-test or Mann-Whitney U test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 119 NSCLC patients, including 59 women (49.6%) and 60 men (50.4%), with a median age of 57. There were 68 patients (57.1%) with EGFR mutations, 19 patients (16%) with KRAS mutations, and 58 patients (48.7%) with TP53 mutations. multi-IHC results showed that, EGFR mutation Vs EGFR wild type samples, (1) the number and proportion of CD8+ T cells in tumor were not statistically different. The median number of CD8+ T cells in tumor stroma was 231.5 vs 359, p = 0.05 and the proportion of CD8+ T cells was 3.92% vs 5.64%, p = 0.02; (2) The median number of macrophage in tumors was 1522 vs 110, p < 0.01, and the proportion of macrophage cells was 24.93% Vs 1.38%, p < 0.01. The median value of macrophages in tumor stroma was 617.5 Vs 208, p < 0.01, and the proportion of macrophages cells was 10.88% vs 3.03%, p < 0.01. Conclusions: Compared with EGFR wild-type patients, EGFR mutation patients have a lower proportion of CD8+ T cells and a higher proportion of macrophages in the immune microenvironment.

scholarly journals Differences in Immunological Landscape between EGFR-Mutated and Wild-Type Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jia-Wei Luo ◽  
Yan-Hua Guo ◽  
Feng-Ying Wu ◽  
Xue-Fei Li ◽  
Xue-Cheng Sun ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Disease Free Survival ◽  
Egfr Mutations ◽  
Wild Type ◽  
Egfr Mutant

Recent clinical trials of lung adenocarcinoma with immune checkpoint inhibitors revealed that lung adenocarcinoma patients with EGFR mutations have a poor response to immunotherapy. However, the mechanisms have not been addressed. We performed immunohistochemistry analyses of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate and compare the characteristics of the tumor microenvironment (TME). We retrospectively enrolled a total of 323 lung adenocarcinoma patients (164 had EGFR mutations), and their corresponding tissue samples were analyzed by the EGFR mutation test and immunohistochemistry. We selected the markers of the immune checkpoint molecule (PD1, PD-L1, and LAG-3) and immune cell (CD3, CD4, CD8, and Foxp3) as markers of the tumor microenvironment. Our results revealed that patients had a distinct tumor microenvironment between EGFR-mutant and wild-type lung adenocarcinomas; the expression of CD3, CD4, PD-L1, and Foxp3 in EGFR-mutant tumors was significantly higher than that in wild-type tumors, while the expression of LAG3 and PD-1 showed a positive correlation with EGFR-wild-type tumors. In survival analysis, EGFR-wild-type patients had longer disease-free survival (DFS) than EGFR-mutant patients ( P = 0.0065 ). Our research demonstrates significant differences in tumor microenvironment composition between EGFR-mutant and wild-type patients. Our findings provide novel evidence that contributes to understanding the mechanism underlying the poor efficacy of immune checkpoint inhibitors.

scholarly journals Efficacy of gefitinib and radiotherapy combination in Indonesian patients with lung adenocarcinoma

2018 ◽  
Vol 56 (3) ◽  
pp. 173-181
Author(s):  
Elisna Syahruddin ◽  
Aida Lufti Huswatun ◽  
Ari Prabowo ◽  
Jamal Zaini ◽  
Fariz Nurwidya ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Point Mutation ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Superior Vena ◽  
Vena Cava ◽  
Egfr Mutations ◽  
Radio Therapy ◽  
Egfr Mutant

Abstract Introduction. Combinations of gefitinib and radiotherapy have been observed to have synergistic and anti-proliferative effects on lung cancer in vitro. In the clinical setting, patients who presented with respiratory difficulties such as superior vena cava syndrome (SVCS), radiotherapy should be given immediately to address the emergency while waiting for the results of epidermal growth factor receptor (EGFR) mutation test. However, there has been no study that described the role of radio-therapy in Indonesian patients with EGFR-mutant lung adenocarcinoma. Methods. This preliminary study aimed to evaluate the efficacy and toxicities of gefitinib and radiotherapy combination in lung adenocarcinoma patients in Persahabatan National Respiratory Referral Hospital, Jakarta, Indonesia. Subjects were consecutively recruited between January 2013 and December 2016. Results. Thirty-one lung adenocarcinoma with EGFR mutations were enrolled. Most of them were male (51.61%) with a median age of 54.5 years old (range 38-70 years old). EGFR mutation characteristics were on exon 21 L858R point mutation (61.30%), exon 21 L861Q point mutation (16.12%) and exon 19 deletion (22.58%). Radiotherapy was given at doses between 30-60 Gy. Among these subjects, median progression-free survival (PFS) was 185 days (95%CI; 123.69 – 246.30), 1-year survival rate (1-yr) was 45.2%, and median overall survival (OS) was 300 days (95%CI; 130.94 – 469.06). There were no grade 3/4 hematological and nonhematological toxicities recorded. The most frequent grade 1 and 2 non-hematological toxicities were skin rash, diarrhea, and paronychia that might be related to tyrosine kinase inhibitor (TKI). Conclusion. The combination of TKI with radiation may be considered in EGFR-mutant lung adenocarcinoma subjects.

scholarly journals Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1327
Author(s):  
Wei-Teing Chen ◽  
Yu-Huei Lin ◽  
Chih-Ying Changchien ◽  
Ying Chen ◽  
Hsin-Han Chang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Pleural Fluid ◽  
Kinase Inhibitor ◽  
Target Therapy ◽  
Advanced Lung Cancer ◽  
Wild Type ◽  
Kaplan Meier ◽  
Egfr Expression ◽  
Mutant Egfr

Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients.

scholarly journals Effect of WW Domain-Containing Oxidoreductase Gene Polymorphism on Clinicopathological Characteristics of Patients with EGFR Mutant Lung Adenocarcinoma in Taiwan

2021 ◽  
Vol 18 (24) ◽  
pp. 13136
Author(s):  
Ju-Pi Li ◽  
Jinghua Tsai Chang ◽  
Po-Chung Ju ◽  
Ming-Hong Hsieh ◽  
Yu-Hua Chao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Genotype Distribution ◽  
Nucleotide Polymorphisms ◽  
Primary Tumors ◽  
Ww Domain ◽  
Significant Difference ◽  
Egfr Mutant

Lung adenocarcinoma is the most common histological type of non-small cell lung cancer, which accounts for the majority of lung cancers. Previous studies have showed that dysregulation of WW domain-containing oxidoreductase (WWOX) participates in the generation of several cancer types, including lung cancer. However, whether these WWOX polymorphisms are related to the clinical risk of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is worthy of investigation. The present study examined the relationship between the WWOX single-nucleotide polymorphisms (SNPs; rs11545028, rs12918952, rs3764340, rs73569323, and rs383362) and the clinicopathological factors in lung adenocarcinoma patients with or without EGFR mutations. We found that there was no significant difference in the genotype distribution of WWOX polymorphism between EGFR wild-type and EGFR mutant in patients with lung adenocarcinoma. Our results demonstrated that the presence of at least one G genotype (CG and GG) allele on WWOX rs3764340 was associated with a significantly higher risk of nearby lymph node involvement in those patients harboring EGFR mutations (odds ratio (OR) = 3.881, p = 0.010) compared with the CC genotype. Furthermore, in the subgroup of lung adenocarcinoma patients with the EGFR-L858R mutation, both WWOX rs3764340 C/G (OR = 5.209, p = 0.023) and rs73569323 C/T polymorphisms (OR = 3.886, p = 0.039) exhibited significant associations with the size of primary tumors and the invasion of adjacent tissues. In conclusion, these data indicate that WWOX SNPs may help predict tumor growth and invasion in patients with EGFR mutant lung adenocarcinoma, especially those with the EGFR-L858R mutant in Taiwan.

K-ras and EGFR mutations in 24 Chinese patients with non-small-cell lung cancer (NSCLC) treated with gefitinib

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17109-17109
Author(s):  
Z. Wang ◽  
Y. Wu ◽  
G. Zhang ◽  
J. Lin ◽  
Q. Zhou ◽  
...  
Keyword(s):  
Disease Control ◽  
Objective Response ◽  
Chinese Patients ◽  
Egfr Mutations ◽  
Reaction Products ◽  
Wild Type ◽  
Nested Polymerase Chain Reaction ◽  
Ras Mutation ◽  
Mutational Status ◽  
Mutant Egfr

17109 Background: It was previously reported that K-ras mutations could behave as a resistance marker for response to gefitinib while EGFR mutations make NSCLC more responsive to this medication. And it is known that Asians and Westerners have different responses to gefitinib. Therefore, we are to identify the mutational status of K-ras and EGFR in the group of Chinese patients with NSCLC especially adenocarcinoma treated with gefitinib to find some helpful information. Methods: Genomic DNA was extracted from tumor specimens, including liquid nitrogen frozen tumor, paraffin blocks and fine needle biopsies from 24 patients with advanced NSCLC, who failed at least one platinum-based regimen, treated with gefitinib. Nested polymerase chain reaction products of codons 12, 13, 59, and 61 of K-ras and exon 18 through 21 of EGFR were directly sequenced at least twice. Results: Patients’ age ranges from 24 to 71 years (54.8 ± 10.2). Male/female was 14/10. Thirteen patients were smokers and 11 were non-smokers. Eighteen were adenocarcinomas, 2 were bronchioloalveolar carcinomas, 2 were squamous cell carcinomas and 2 were large cell carcinomas. The disease control (CR+PR+SD) rate was 79.2% (19/24) and the objective response (CR+PR) rate was 50.0% (12/24). No K-ras gene mutation was found in all patients. Fifteen patients (62.5%, 15/24) harbored EGFR mutations, which were delE746-A750 (8), delE746-A751 (1), delE746-A751insA (1), L861Q (1), L858R (5) and A871G (1). Two patients had double mutations (delE746-A750 and L858R). The disease control rate for wild type and mutant EGFR were 66.7% (6/9) and 86.7% (13/15), and the objective response rate were 33.3% (3/9) and 60.0% (9/15). Median time to progress (TTP) for wild type and mutant EGFR were 439 days (SE 249.8) and 367 days (SE 108.8). However, no statistically significant differences were found between these two groups regarding the response rates and TTP. Conclusions: K-ras mutation may occur at a low frequency in Chinese NSCLC groups despite the pathology, status of smoking, gender and EGFR mutations. And the relationship between the response to gefitinib and K-ras mutation might still remain to be determined at least in Chinese NSCLC. And the role of EGFR mutations in prediction of response to gefitinib should be further studied. No significant financial relationships to disclose.

scholarly journals Genome-wide analysis of microRNA signature in lung adenocarcinoma with EGFR exon 19 deletion

2015 ◽  
Author(s):  
Lixia Ju ◽  
Mingquan Han ◽  
Xuefei Li ◽  
Chao Zhao
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Genetic Alterations ◽  
Egfr Mutations ◽  
Wild Type ◽  
Lung Cancer Patients ◽  
Whole Genome Microarray ◽  
Exon 19 Deletion ◽  
The Difference ◽  
Exon 19

AbstractPurposeThe findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and microRNAs can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer.Materials and methodsIn this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and its wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we have detected the microRNAs expression in serum of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type.ResultsThe expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type.ConclusionsIt is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 can be further explored for potential predictor and targeted biomarker when it is difficult to get the tumors.

Clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20588-e20588
Author(s):  
Linping Gu ◽  
Bei Zhang ◽  
Ding Zhang ◽  
Hong Jian
Keyword(s):  
Lung Adenocarcinoma ◽  
Egfr Mutation ◽  
De Novo ◽  
Egfr Mutations ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Genetic Characteristics ◽  
Egfr Mutant ◽  
Lung Adenocarcinomas ◽  
Egfr T790m

e20588 Background: Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the resistance mechanism of EGFR tyrosine kinase inhibitors. However, the clinical course of transformed SCLC and the difference of genomic profiling between de novo SCLC patients and transformed SCLC patients are still poorly characterized. Methods: Patients from our hospital diagnosed with SCLC were enrolled retrospectively in this study, including de novo SCLC patients and SCLC patients transformed from EGFR-mutant lung adenocarcinomas. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples by next generation sequencing (NGS). In statistical analysis, fisher ‘exact test was used. All tests were bilateral, with P<0.05 indicating significant statistical difference. Results: In total, 16 patients with SCLC transformed from EGFR-mutant lung adenocarcinomas and 230 de novo SCLC patients were included in our study. Transformed SCLC patients were more in younger (p=0.007), female (p<0.001) and non-smokers (p<0.001) than de novo SCLC patients. In transformed SCLC patients, 12 patients (75%) occurred SCLC transformation within 2 years after the lung adenocarcinomas diagnosis. Median transformation time was 20 months. During the treatment of adenocarcinomas, the overall response rate (ORR) was 75% and the median progression-free survival was 12 months. After the initiation of SCLC therapy, the ORR of 1st line chemotherapy was 40%. For the genomic profiling, EGFR mutations, including exon 19 deletion (56%), L858R (38%), and others (6%), were detected. 11 patients with acquired resistance were received EGFR T790M test, 82% of patients had acquired EGFR T790M mutation. 11 patients after transformation to SCLC had NGS test, 100% maintained their founder EGFR mutation, and other recurrent mutations included TP53, RB1 and EGFR amplification. Compared with the genetic alterations in de novo SCLC patients, TP53 mutations were significantly decreased (p=0.006) while EGFR mutations were significantly elevated (p<0.001) in transformed SCLC patients. However, no significant difference on RB1, ALK and ROS1 mutations were observed. Interestingly, a 60-year-old woman in our transformed SCLC cohort harbored EGFR 19 del mutant at allele frequency of 50.39%，she received osimertinib plus epirubicin/cyclophosphamide as 1st line treatment and reached partial response, with survival of 4 years to date. Conclusions: We demonstrated the clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC and found one patient still benefited from EGFR-TKI. Our study suggested that SCLC patients with EGFR mutation who transformed from lung adenocarcinoma may be potential benefit population using EGFR inhibitors.

scholarly journals Concurrent Genetic Alterations and Other Biomarkers Predict Treatment Efficacy of EGFR-TKIs in EGFR-Mutant Non-Small Cell Lung Cancer: A Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Yijia Guo ◽  
Jun Song ◽  
Yanru Wang ◽  
Letian Huang ◽  
Li Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Efficacy ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Egfr Tkis ◽  
Gene Alterations

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit de novo or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (i.e., coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (e.g., PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.

scholarly journals Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3712
Author(s):  
Paola Peinado ◽  
Alvaro Andrades ◽  
Marta Cuadros ◽  
Maria Isabel Rodriguez ◽  
Isabel F. Coira ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Genetic Alterations ◽  
Cell Models ◽  
Functional Studies ◽  
Cellular Models ◽  
Mutational Status

Mammalian SWI/SNF (SWitch/Sucrose Non-Fermentable) complexes are ATP-dependent chromatin remodelers whose subunits have emerged among the most frequently mutated genes in cancer. Studying SWI/SNF function in cancer cell line models has unveiled vulnerabilities in SWI/SNF-mutant tumors that can lead to the discovery of new therapeutic drugs. However, choosing an appropriate cancer cell line model for SWI/SNF functional studies can be challenging because SWI/SNF subunits are frequently altered in cancer by various mechanisms, including genetic alterations and post-transcriptional mechanisms. In this work, we combined genomic, transcriptomic, and proteomic approaches to study the mutational status and the expression levels of the SWI/SNF subunits in a panel of 38 lung adenocarcinoma (LUAD) cell lines. We found that the SWI/SNF complex was mutated in more than 76% of our LUAD cell lines and there was a high variability in the expression of the different SWI/SNF subunits. These results underline the importance of the SWI/SNF complex as a tumor suppressor in LUAD and the difficulties in defining altered and unaltered cell models for the SWI/SNF complex. These findings will assist researchers in choosing the most suitable cellular models for their studies of SWI/SNF to bring all of its potential to the development of novel therapeutic applications.

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