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J Neurol Surg B Skull Base 2024; 85(04): 325-331
DOI: 10.1055/a-2088-6730
Original Article

SMARCB1-Retained and SMARCB1-Deficient SNUC are Genetically Distinct: A Pilot Study Using RNA Sequencing

Chandala Chitguppi
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Marc Rosen
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Gurston Nyquist
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Elina Toskala
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
James Evans
2   Department of Neurological Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Stacey Gargano
3   Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Madalina Tuluc
3   Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Adam Ertel
4   Department of Cancer Biology, Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, United States
,
Glen Dsouza
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Sankar Addya
4   Department of Cancer Biology, Thomas Jefferson University and Sidney Kimmel Cancer Center, Philadelphia, Pennsylvania, United States
,
Jennifer Johnson
5   Department of Hematology and Medical Oncology, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Voichita Bar-Ad
6   Department of Radiation Oncology-Head and Neck Cancer, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
,
Mindy Rabinowitz
1   Department of Otolaryngology and Head and Neck Surgery, Thomas Jefferson University Hospitals, Philadelphia, Pennsylvania, United States
› Author Affiliations Funding This work was supported by the North American Skull Base Society (NASBS) research grant 2020. Data analyses were performed in the Sidney Kimmel Cancer Center Meta-Omics core facility supported by NIH/NCI Support Grant (P30 CA056036).
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Abstract

Background Understanding the genetic basis for the molecular classification of sinonasal undifferentiated carcinoma (SNUC) based on SMARCB1 may improve our understating regarding the nature of the disease. The objective of the study was to compare the genetic profile of SMARCB1-retained (SR-SNUC) and SMARCB1-deficient SNUC (SD-SNUC).

Methods Formalin-fixed, paraffin-embedded tissue from treatment-naive patients with SNUC were selected. Three cases of SR-SNUC, four cases of SD-SNUC, and four samples of nontumor tissue (control samples) were selected. Ribonucleic acid (RNA) sequencing was performed.

Results SR-SNUC had a higher number of variants (1 variant for every 15,000 bases) compared with SD-SNUC (1 variant every 29,000 bases). The ratio of missense to silent mutation ratio was higher for SR-SNUC (0.8) as compared with SD-SNUC (0.7). Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC. The genes that had a higher expression in SR-SNUC included TPD52L1, B3GNT3, GFY, TJP3, ELL3, CYP4F3, ALDH3B2, CKMT1B, VIPR1, SLC7A5, PPP2R2C, UPK3B, MUC1, ELF5, STY7, and H2AC14. The gene that had a higher expression in SD-SNUC was ZFHX4. Most of these genes were related to either protein translation or immune regulation. The most common (n = 3, 75%) mechanisms of loss of SMARCB1 gene in SD-SNUC was loss of heterozygosity.

Conclusion RNA sequencing is a viable and informative approach for genomic profiling of archival SNUC samples. Both SR-SNUC and SD-SNUC were noted to have distinct genetic profiles underlying the molecular classification of these diseases.

Keywords

SMARCB1 - SNUC - RNA sequencing - INI-1 - sinonasal cancer

Presentation

Oral presentation at North American Skull base society (NASBS) annual meeting at Phoenix, Arizona on February 18–20, 2022.




Publication History

Received: 28 January 2023

Accepted: 03 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
12 June 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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