Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma

Alana R Rodney; Zachary L Skidmore; Jennifer K Grenier; Obi L Griffith; Andrew D Miller; Shirley Chu; Faraz Ahmed; Jeffrey N Bryan; Santiago Peralta; Wesley C Warren

doi:10.3389/fvets.2023.1079019

Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma

Front Vet Sci. 2023 May 17:10:1079019. doi: 10.3389/fvets.2023.1079019. eCollection 2023.

Authors

Affiliations

¹ Department of Animal Sciences, University of Missouri, Columbia, MO, United States.
² McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, United States.
³ Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
⁴ Department of Oncology, School of Veterinary Medicine, University of Missouri, Columbia, MO, United States.
⁵ Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

Abstract

Feline oral squamous cell carcinoma (FOSCC) is a cancer of the squamous cell lining in the oral cavity and represents up to 80% of all oral cancers in cats, with a poor prognosis. We have used whole exome sequencing (WES) and RNA sequencing of the tumor to discover somatic mutations and gene expression changes that may be associated with FOSCC occurrence. FOSCC offers a potential comparative model to study human head and neck squamous cell carcinoma (HNSCC) due to its similar spontaneous formation, and morphological and histological features. In this first study using WES to identify somatic mutations in feline cancer, we have identified tumor-associated gene mutations in six cats with FOSCC and found some overlap with identified recurrently mutated genes observed in HNSCC. Four samples each had mutations in TP53, a common mutation in all cancers, but each was unique. Mutations in other cellular growth control genes were also found such as KAT2B and ARID1A. Enrichment analysis of FOSCC gene expression profiles suggests a molecular similarity to human OSCC as well, including alterations in epithelial to mesenchymal transition and IL6/JAK/STAT pathways. In this preliminary study, we present exome and transcriptome results that further our understanding of FOSCC.

Keywords: cancer; feline oral squamous cell carcinoma; human head and neck cancer; variant calling comparisons; whole exome sequencing.

Grants and funding

This work was funded in part by the EveryCat Foundation under Award Number W21 002 (to SC). OG was supported by the National Cancer Institute (NCI) of the NIH under Award Number K22CA188163 and by the Siteman Cancer Center and The Foundation for Barnes-Jewish Hospital. The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.