Characterizing the mutational landscape of sinonasal squamous cell carcinoma using whole-exome sequencing

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.

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.

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.

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.