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

• Type of Material: Article
• Authors: Deli Liu, University of Georgia; Huan Xiong, University of Georgia; Angela E. Ellis, University of Georgia; Nicole C. Northrup, University of Georgia; Kevin K. Dobbin, University of Georgia; Dong Shin, Emory University; Shaying Zhao, University of Georgia
• Language: English
• Date: 2015-06-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Liu et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pgen.1005277
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 11
• Issue: 6
• Start Page: e1005277
• End Page: e1005277
• Grant/Funding Information: his work was supported by the National Cancer Institute (NCI) R01 CA182093 (to SZ) and the AKC Canine Health Foundation (www.akcchf.org) (to SZ), as well as by pilot project funds from the NCI P50 CA128613 (PI: DMS).; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: OSTEOSARCOMA; MOUSE; EXPRESSION; MODELS; Genetics & Heredity; Life Sciences & Biomedicine; Science & Technology; DOMESTIC DOGS; GENOMIC CHARACTERIZATION; HUMAN-PAPILLOMAVIRUS; DNA; HUMAN CANCER; BIOLOGY
• Research Categories: Health Sciences, Oncology; Biology, Molecular; Biology, Genetics

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.