Herein we report a proof-of-principle study illustrating a novel dog-human 
comparison strategy that addresses a central aim of cancer research, namely 
cancer driver-passenger distinction. We previously demonstrated that sporadic 
canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms 
as their human counterparts. In this study, we compared the genome-wide copy 
number abnormalities between 29 human and 10 canine sporadic CRCs. This led to 
the identification of 73 driver candidate genes (DCGs), altered in both species, 
and with 27 from the whole genome and 46 from dog-human genomic rearrangement 
breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), 
altered in humans only and located in GRB regions. We noted that DCGs 
significantly differ from PCGs in every analysis conducted to assess their 
cancer relevance and biological functions. Importantly, although PCGs are not 
enriched in any specific functions, DCGs possess significantly enhanced 
functionality closely associated with cell proliferation and death regulation, 
as well as with epithelial cell apicobasal polarity establishment/maintenance. 
These observations support the notion that, in sporadic CRCs of both species, 
cell polarity genes not only contribute in preventing cancer cell invasion and 
spreading, but also likely serve as tumor suppressors by modulating cell growth. 
This pilot study validates our novel strategy and has uncovered four new 
potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, 
DENND5A and AVL9). Expansion of this study would make more driver-passenger 
distinctions for cancers with large genomic amplifications or deletions, and 
address key questions regarding the relationship between cancer pathogenesis and 
epithelial cell polarity control in mammals.