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

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Sinonasal undifferentiated carcinoma (SNUC) classification benefits from understanding its genetic basis.
• SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1) status is key for molecular subtyping.
• Comparing SMARCB1-retained (SR-SNUC) and SMARCB1-deficient (SD-SNUC) SNUC provides insight into disease nature.

Purpose of the Study:

• To compare the genetic profiles of SR-SNUC and SD-SNUC.
• To identify distinct genetic markers for SNUC molecular classification.

Main Methods:

• RNA sequencing was performed on formalin-fixed, paraffin-embedded tissues.
• Samples included treatment-naive SNUC patients: 3 SR-SNUC, 4 SD-SNUC, and 4 non-tumor controls.
• Genetic variants and gene expression were analyzed.

Main Results:

• SR-SNUC exhibited a higher variant frequency (1 per 15kb) than SD-SNUC (1 per 29kb).
• Approximately 1,500 genes were differentially expressed between SR-SNUC and SD-SNUC, with distinct genes related to protein translation and immune regulation.
• Loss of heterozygosity was the most common mechanism for SMARCB1 loss in SD-SNUC.

Conclusions:

• RNA sequencing is effective for genomic profiling of archival SNUC samples.
• SR-SNUC and SD-SNUC possess distinct genetic profiles.
• These findings support molecular classification of SNUC based on SMARCB1 status.