Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients

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 t...

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Main Authors: Subasri Armon, Paul Hofman, Marius Ilié
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/8/1920
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spelling doaj-63a43bc6c3d64b92812bd2ea13651d832021-08-26T13:37:05ZengMDPI AGCells2073-44092021-07-01101920192010.3390/cells10081920Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer PatientsSubasri Armon0Paul Hofman1Marius Ilié2Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, Université Côte d’ Azur, 06000 Nice, FranceLaboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, Université Côte d’ Azur, 06000 Nice, FranceLaboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank (BB-0033-00025), Nice Hospital University, FHU OncoAge, Université Côte d’ Azur, 06000 Nice, FranceLung 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 <i>SMARCA4</i> gene. <i>SMARCA4</i>-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying <i>SMARCA4</i>-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 <i>SMARCA4</i> 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 <i>KRAS</i>, <i>KEAP1</i>, and <i>STK11,</i> 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 <i>SMARCA4</i>-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of <i>SMARCA4</i>, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of <i>SMARCA4</i> 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 <i>SMARCA4</i> are trending; hence, awareness of pathologists and clinicians is needed for the <i>SMARCA4</i>-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients.https://www.mdpi.com/2073-4409/10/8/1920non-small cell lung carcinoma<i>SMARCA4</i> genesolid adenocarcinomaimmunohistochemistrysequencing
collection DOAJ
language English
format Article
sources DOAJ
author Subasri Armon
Paul Hofman
Marius Ilié
spellingShingle Subasri Armon
Paul Hofman
Marius Ilié
Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
Cells
non-small cell lung carcinoma
<i>SMARCA4</i> gene
solid adenocarcinoma
immunohistochemistry
sequencing
author_facet Subasri Armon
Paul Hofman
Marius Ilié
author_sort Subasri Armon
title Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
title_short Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
title_full Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
title_fullStr Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
title_full_unstemmed Perspectives and Issues in the Assessment of <i>SMARCA4</i> Deficiency in the Management of Lung Cancer Patients
title_sort perspectives and issues in the assessment of <i>smarca4</i> deficiency in the management of lung cancer patients
publisher MDPI AG
series Cells
issn 2073-4409
publishDate 2021-07-01
description 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 <i>SMARCA4</i> gene. <i>SMARCA4</i>-deficient adenocarcinomas are preponderant in younger aged male smokers with a predominant solid morphology. The importance of identifying <i>SMARCA4</i>-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 <i>SMARCA4</i> 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 <i>KRAS</i>, <i>KEAP1</i>, and <i>STK11,</i> 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 <i>SMARCA4</i>-deficient adenocarcinoma, as it carries worse repercussions on patient survival, despite having an exceptionally low prevalence. Herein, we discuss the pathophysiology of <i>SMARCA4</i>, the clinicopathological consequences, and different detection methods, highlighting the perspectives and challenges in the assessment of <i>SMARCA4</i> 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 <i>SMARCA4</i> are trending; hence, awareness of pathologists and clinicians is needed for the <i>SMARCA4</i>-dNSCLC entity with close follow-up on new management strategies to overcome the poor possibilities of survival in such patients.
topic non-small cell lung carcinoma
<i>SMARCA4</i> gene
solid adenocarcinoma
immunohistochemistry
sequencing
url https://www.mdpi.com/2073-4409/10/8/1920
work_keys_str_mv AT subasriarmon perspectivesandissuesintheassessmentofismarca4ideficiencyinthemanagementoflungcancerpatients
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AT mariusilie perspectivesandissuesintheassessmentofismarca4ideficiencyinthemanagementoflungcancerpatients
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