Abstract PR08: Man's best friend for cancer driver-passenger discrimination

Abstract

Abstract Spontaneously occurring canine cancer represents one of the best cancer models. Herein we report a novel dog human comparison strategy that utilizes inter-species genomic arrangements occurring during the past >75 million years to tackle a central aim of cancer research, namely cancer driver passenger discrimination. After showing that spontaneous canine colorectal cancers share similar molecular pathogenesis mechanisms as their human counterparts (Tang et al., 2010; Youmans et al., 2012), we compared copy number abnormalities between the two species (Tang et al., 2013). This led to the identification of 73 driver candidate genes (DCGs) and 38 passenger candidate genes (PCGs). Importantly, DCGs differ from PCGs in every analysis conducted to assess their cancer relevance. Moreover, while PCGs' functions appear random, DCGs' are significantly associated with cell proliferation and epithelial cell polarities. We are conducting 3D culture to validate these functions, leading to the discovery of several new tumor suppressors and cell polarity genes. Besides colorectal cancer, we have also successfully applied this dog-human comparison strategy on triple negative breast cancers, of which copy number abnormalities are extensive. In summary, we have developed a novel approach to efficiently analyze the massive cancer genomic data generated by TCGA and others for cancer driver discovery. Tang, J., Le, S., Sun, L., Yan, X., Zhang, M., Macleod, J., Leroy, B., Northrup, N., Ellis, A., Yeatman, T. J., et al. (2010). Copy number abnormalities in sporadic canine colorectal cancers. Genome research 20, 341-350. Tang, J., Li, Y., Lyon, K., Camps, J., Dalton, S., Ried, T., and Zhao, S. (2013). Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer. Oncogene. Youmans, L., Taylor, C., Shin, E., Harrell, A., Ellis, A. E., Seguin, B., Ji, X., and Zhao, S. (2012). Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors. PloS one 7, e50813. This abstract is also presented as Poster B51. Citation Format: Shaying Zhao. Man's best friend for cancer driver-passenger discrimination. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr PR08.