ICCFGG 2022
#1 A multiomic case study of feline oral squamous cell carcinoma Alana R. Rodney 1 , Shirley Chu2, Zach Skidmore3, Jennifer K. Grenier4, Obi L. Griffith3, Jeffery Bryan2, Andrew D. Miller4, Santiago Peralta5, Wesley C. Warren1,6 arrpb6@mail.missouri.edu 1Department of Animal Sciences, University of Missouri, Columbia, MO, USA; 2Department of Veterinary Medicine and Surgery, School of Veterinary Medicine, University of Missouri, Columbia, MO, USA; 3McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA; 4Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 5Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 6Institute for Data Science and Informatics, Department of Surgery, School of Medicine, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA Rarer occurring solid tumors in the domestic cat offer a comparative contradiction to the more common occurrence in dogs and humans. Feline oral squamous cell carcinoma (FOSCC) rep- resents up to 80% of all oral cancers in cats. The vast majority of FOSCCs are extremely locally invasive with a poor prognosis despite multimodal treatment. FOSCC shares many similar clinical characteristics to human head and neck squamous cell carcinomas (HNSCC), which also present therapeutic challenges. In contrast to humans, the etiology and driver genes are largely unknown. We performed WES on six matched tumor and normal samples to discover somatic mutations that may be potential drivers and investigated gene expression in FOSCC tumors with RNA-seq. Our WES results show mutations in driver genes in common with HNSCC. However, the only recurrently mutated gene thus far was TP53, the most common mutation seen in HPV- HNSCC. A single cat had a missense mutation in ARID1A, a protein that functions as a tumor stemness repressor by disrupting the perturbed function of p53 or PTEN pathways but further study is needed to estimate its contribution to FOSCC as well as other non-recurrent mutations discovered in this preliminary study. Tumor mutation burden (TMB) as a classifier for response to immunotherapy has not been evaluated in feline tumors to our knowledge but we found that FOSCC had similar TMB range to earlier studies of HNSCC but further work to assess its importance is also needed. Overall, func- tional enrichment analysis of gene expression profiles showed molecular similarity to HNSCC as well as upregulation of canonical oncogenic pathways, including epithelial to mesenchymal transi- tion and IL6/JAK/STAT pathways. #2 Genetics of Acral Mutilation Syndrome in several dog breeds equivalent to human sensory neuropathies Anna Letko1 , Pascale Quignon1,Catherine André1 anna.letko@univ-rennes1.fr Institut de Génétique et Développement de Rennes (IGDR), University Rennes1, Brittany, France Canine acral mutilation syndrome (AMS) has been documented for decades as part of inherited sensory neuropathies and has clinical similarities to human hereditary sensory autonomic neurop- athies (HSAN), including decrease/loss of tactile and pain sensation, which leads to skin ulceration and severe auto-amputation of digits. Although the disorder was reported in several dog breeds, causal variants in only two genes were identified to date, suggesting larger genetic heterogeneity. In humans, 16 genes have been associated with HSAN but also do not explain the disease origin of all patients. Our aim is to characterize the underlying genetic etiology leading to AMS in dogs, as natural models for HSAN.
54
Made with FlippingBook - Online magazine maker