Related Experiment Video
Updated: Jan 17, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Characterizing the mutational landscape of sinonasal squamous cell carcinoma using whole-exome sequencing
Jimmy A Vareta1, Xiang Zhang2, Damaris Kuhnell3
1Division of Hematology & Oncology, University of Vermont Larner College of Medicine, Burlington, VT, United States; University of Vermont Cancer Center, Burlington, VT, United States.
Background:
Sinonasal squamous cell carcinoma (SNSCC) accounts for less than 3% of all head and neck cancers. The 5-year overall survival rate ranges from 30 to 50%. While whole-exome sequencing (WES) studies have illuminated the mutational landscape of numerous cancer types, few systematic efforts have been conducted for SNSCC, leaving many common driver mutations in this malignancy largely unknown. The objective of this study was to address this gap in knowledge by comprehensively cataloging somatic mutations arising in SNSCC through WES.
Patients And Methods:
This was a retrospective study in which WES was performed on OCT-embedded tumor tissue and paired adjacent normal tissue from 12 patients diagnosed with incident SNSCC at the University of Cincinnati Cancer Center from 2012 to 2014.
Results:
We identified 263 genes that harbored two or more coding region somatic mutations in multiple SNSCC tumors. Eight genes were significantly mutated (q < 0.1). TP53 was the most frequently mutated gene (6/12; 50 %). The other 7 significantly mutated genes included NOTCH1 (4/12; 33.3 %), KMT2D (4/12; 33 %), VWDE (4/12; 33 %), FNBP4 (3/12; 25 %), SCAND3 (3/12; 25 %), NOD1 (3/12; 25 %) and OR5C1 (2/12; 17 %). Somatic mutations observed in these genes included truncating or non-synonymous variants in functional domains that may affect regulation of apoptosis, NOTCH signaling, cell cycle, and epithelial cell proliferation, and epigenetic regulation of gene expression.
Conclusion:
This study helps elucidate the mutational landscape of SNSCC, advancing our understanding of potential driver mutations and yielding potential new therapeutic avenues for management of these devastating malignancies.
Insights
This study identified key genetic mutations in sinonasal squamous cell carcinoma (SNSCC), revealing potential new therapeutic targets. Understanding these mutations in SNSCC is crucial for improving patient survival rates.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Sinonasal squamous cell carcinoma (SNSCC) is a rare cancer with poor survival rates.
- Limited genomic data exists for SNSCC, hindering the identification of driver mutations.
- Whole-exome sequencing (WES) offers a powerful approach to uncover the genetic underpinnings of rare cancers.
Purpose of the Study:
- To comprehensively catalog somatic mutations in SNSCC using WES.
- To identify frequently mutated genes and potential driver mutations in SNSCC.
- To advance the understanding of SNSCC pathogenesis and identify therapeutic targets.
Main Methods:
- Retrospective analysis of WES data from 12 SNSCC patients.
- Comparison of tumor tissue with adjacent normal tissue to identify somatic mutations.
- Statistical analysis to identify significantly mutated genes (q < 0.1).
Main Results:
- Identified 263 genes with recurrent somatic mutations in SNSCC.
- Eight genes were significantly mutated, including TP53 (50%), NOTCH1 (33.3%), and KMT2D (33.3%).
- Mutations affected key cellular processes like apoptosis, cell cycle, and gene expression.
Conclusions:
- This WES study elucidates the mutational landscape of SNSCC.
- Identified potential driver mutations provide new insights into SNSCC development.
- Findings may lead to novel therapeutic strategies for SNSCC management.
