Abstract 5147: Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level

Abstract

Abstract Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better utilize this valuable resource, we performed 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 faithfully recapitulate many key molecular features of human HNSCC. These include similar genomic copy number abnormality landscapes, analogous sequence mutation patterns, and recurrent alteration of known HNSCC genes (e.g., MYC, CDKN2A) and pathways (e.g., cell cycle, mitogenic signaling, TGFβ signaling). Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI are also prominent in these canine tumors. The strong dog-human molecular homology fundamentally justifies the use of our novel dog-human comparison strategy for driver-passenger discrimination for HNSCC. This cross-species comparison will significantly advance beyond the current findings with the massive genomic data of the cancer genome atlas (TCGA), as exemplified by our pilot study on human 8q, a recurrently amplified site in human HNSCC. HNSCC represents the sixth leading cancer by incidence in humans; thus developing effective therapeutic interventions is important. While our understanding of the biology of HNSCC has been greatly advanced over past decades, translating these findings into clinical success has been frustratingly slow. A significant obstacle is the lack of translational model that can bridge the gap between preclinical research and human clinical trials. Our study indicates that spontaneous canine HSCC can effectively bridge this gap, significantly accelerating anti-HNSCC drug discovery. Note: This abstract was not presented at the meeting. Citation Format: Deli Liu, Huan Xiong, Angela E. Ellis, Nicole C. Northrup, Dong M. Shin, Shaying Zhao. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5147. doi:10.1158/1538-7445.AM2015-5147