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Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients

1
Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, Université Côte d’ Azur, 06000 Nice, France
2
Histopathology Unit, Department of Pathology, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur 50586, Malaysia
*
Author to whom correspondence should be addressed.
Academic Editor: Lucas Treps
Cells 2021, 10(8), 1920; https://doi.org/10.3390/cells10081920
Received: 21 June 2021 / Revised: 21 July 2021 / Accepted: 26 July 2021 / Published: 29 July 2021
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Lung Cancers)
Lung cancers are ranked third among the cancer incidence in France in the year 2020, with adenocarcinomas being the commonest sub-type out of ~85% of non-small cell lung carcinomas. The constant evolution of molecular genotyping, which is used for the management of lung adenocarcinomas, has led to the current focus on tumor suppressor genes, specifically the loss of function mutation in the SMARCA4 gene. SMARCA4-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying SMARCA4-deficient adenocarcinomas has gained interest for lung cancer management due to its aggressive behavior at diagnosis with vascular invasion and metastasis to the pleura seen upon presentation in most cases. These patients have poor clinical outcome with short overall survival rates, regardless of the stage of disease. The detection of SMARCA4 deficiency is possible in most pathology labs with the advent of sensitive and specific immunohistochemical antibodies. The gene mutations can be detected together with other established lung cancer molecular markers based on the current next generation sequencing panels. Sequencing will also allow the identification of associated gene mutations, notably KRAS, KEAP1, and STK11, which have an impact on the overall survival and progression-free survival of the patients. Predictive data on the treatment with anti-PD-L1 are currently uncertain in this high tumor mutational burden cancer, which warrants more groundwork. Identification of target drugs is also still in pre-clinical testing. Thus, it is paramount to identify the SMARCA4-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of SMARCA4, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of SMARCA4 deficiency for the management of non-small cell lung cancer patients. This is imperative, as the contemporary shift on identifying biomarkers associated with tumor suppressor genes such as SMARCA4 are trending; hence, awareness of pathologists and clinicians is needed for the SMARCA4-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients. View Full-Text
Keywords: non-small cell lung carcinoma; SMARCA4 gene; solid adenocarcinoma; immunohistochemistry; sequencing non-small cell lung carcinoma; SMARCA4 gene; solid adenocarcinoma; immunohistochemistry; sequencing
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MDPI and ACS Style

Armon, S.; Hofman, P.; Ilié, M. Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients. Cells 2021, 10, 1920. https://doi.org/10.3390/cells10081920

AMA Style

Armon S, Hofman P, Ilié M. Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients. Cells. 2021; 10(8):1920. https://doi.org/10.3390/cells10081920

Chicago/Turabian Style

Armon, Subasri, Paul Hofman, and Marius Ilié. 2021. "Perspectives and Issues in the Assessment of SMARCA4 Deficiency in the Management of Lung Cancer Patients" Cells 10, no. 8: 1920. https://doi.org/10.3390/cells10081920

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