SMARCA4/BRG1-Deficient Non-Small Cell Lung Carcinomas: A Case Series and Review of the Literature

Arch Pathol Lab Med. 2021 Jan 1;145(1):90-98. doi: 10.5858/arpa.2019-0633-OA.


Context.—: Somatic mutations in SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or BRG1 (Brahma-related gene 1) loss identifies a subset of non-small cell lung carcinomas (NSCLCs) lacking alterations in EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 (ROS proto-oncogene 1) genes. Preliminary observations suggest responsiveness to immunotherapy and targeted therapies.

Objective.—: To study BRG1 loss in NSCLCs and elucidate the clinicopathologic profile of such SMARCA4-deficient NSCLCs.

Design.—: Non-small cell lung carcinomas diagnosed during 6 years were subject to immunohistochemistry for BRG1 and BRM (Brahma). Tumors with BRG1 loss were stained with antibodies against thyroid transcription factor 1 (TTF-1), p40, cytokeratins, hepatocyte paraffin 1 (Hep Par 1), Sal-like protein 4 (SALL4), CD34, SRY-box 2 (SOX2), chromogranin, synaptophysin, p53, integrase interactor 1, ALK, and ROS1. EGFR mutation testing was performed by polymerase chain reaction-based method.

Results.—: Among 100 NSCLCs tested, 4 cases (4%) showed BRG1 loss. The histology ranged from solid adenocarcinomas (n = 1) to large cell/poorly differentiated carcinomas (n = 3) with clear cell cytology in 2 cases. All showed loss/reduction of BRM with variable cytokeratin and SALL4 expression, and were negative for TTF-1, p40, Hep Par 1, ALK, ROS1, and EGFR mutations. CD34 and SOX2 were negative in all 4 cases. Isolated BRM loss was common (21%), distributed across all NSCLC subtypes including squamous cell carcinomas and a hepatoid adenocarcinoma.

Conclusions.—: BRG1 loss occurs in a subset of TTF-1/p40-negative poorly differentiated NSCLCs. Identification and follow-up will clarify the prognosis, diagnostic criteria, and potential for therapeutic personalization.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • DNA Helicases / deficiency*
  • DNA Helicases / genetics
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Nuclear Proteins / deficiency*
  • Nuclear Proteins / genetics
  • Proto-Oncogene Mas
  • Retrospective Studies
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics


  • MAS1 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Mas
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases