Canine Spontaneous Head and Neck Squamous Cell Carcinomas Represent Their Human Counterparts at the Molecular Level

Abstract

Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial–mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

Sequence analysis ofRASandRAFmutation hot spots in canine carcinoma

“…Oncogenic HRAS activates MAPK and phosphatidylinositol 3‐kinase (PI3K) signaling cascade, two effector pathways important for carcinogenesis . The presence of HRAS mutations in canine oral SCC is consistent with a recent study demonstrating similar molecular signatures in canine and human SCC including overexpression of these pathway molecules . Along with many anatomical, histological and clinical features shared between human and canine oral SCCs, these molecular similarities suggest that dog may serve as a comparable spontaneous cancer model for human head and neck SCC.…”

Development and Validation of a Clinically Relevant Workflow for MR-Guided Volumetric Arc Therapy in a Rabbit Model of Head and Neck Cancer

“…While mouse models are widely utilized in research, the clinical or translational value of radiation studies in murine systems remains unclear. As a result, there has been increased interest in developing and applying canine (dogs), feline (cats), and leporine (rabbits) models of cancer for preclinical research [21][22][23][24][25][26][27]. However, the literature on the implementation of IG-VMAT in large animal models of cancer, especially HNSCC, is limited.…”

“…Similarly, in the head and neck region, differences in salivary gland anatomy between rodents and humans exist that should be considered in the context of RT treatment planning and toxicity assessment [20]. Given these limitations of small animal models, there has been increased interest in the utilization of large animal models of HNSCC for preclinical studies [21][22][23]. In this regard, we have recently reported on a novel orthotopic rabbit model of HNSCC based on surgical transplantation of Shope cottontail rabbit papilloma virus associated VX2 tumors into the neck of rabbits [24].…”

A Kmer-based paired-end read (KPR)de novoassembler and genotyper to genotype major histocompatibility complex class I (MHC-I) alleles for the dog

“…We applied our KPR assembler ( Figure 1) to our canine RNA-seq data, 27 to 87 million pairedend reads of 76x76bp or 50x50bp each of dogs with various cancers 19,[26][27][28] . We then performed Sanger sequencing on 13 samples to validate the assembled contigs.…”