Articulo cientifico genetica animal

Downloaded from genome.cshlp.org on November 13, 2011 - Published by Cold Spring Harbor Laboratory Press

Copy number abnormalities in sporadic canine colorectal cancers
Jie Tang, Shoshona Le, Liang Sun, et al. Genome Res. 2010 20: 341-350 originally published online January 19, 2010 Access the most recent version at doi:10.1101/gr.092726.109

Supplemental Material Referenceshttp://genome.cshlp.org/content/suppl/2010/01/19/gr.092726.109.DC1.html This article cites 50 articles, 15 of which can be accessed free at: http://genome.cshlp.org/content/20/3/341.full.html#ref-list-1 Article cited in: http://genome.cshlp.org/content/20/3/341.full.html#related-urls

Email alerting service

Receive free email alerts when new articles cite this article - sign up in the box at the topright corner of the article or click here

To subscribe to Genome Research go to: http://genome.cshlp.org/subscriptions

Copyright © 2010 by Cold Spring Harbor Laboratory Press

Downloaded from genome.cshlp.org on November 13, 2011 - Published by Cold Spring Harbor Laboratory Press

Letter

Copy number abnormalities in sporadic canine colorectal cancers
Jie Tang,1 Shoshona Le,2 Liang Sun,3Xiuzhen Yan,1 Mucheng Zhang,1 Jennifer MacLeod,4 Bruce LeRoy,5 Nicole Northrup,5 Angela Ellis,5 Timothy J. Yeatman,6 Yanchun Liang,3 Michael E. Zwick,2 and Shaying Zhao1,7
Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia 30602, USA; Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30602, USA;3College of Computer Science and Technology, Jilin University, Changchun 130021, China; 4School of Veterinary Medicine, University of California Davis, California 95616, USA; 5College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602, USA; 6Departments of Surgery, Pathology, and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
2 1Human colorectal cancer (CRC) is one of the better-understood systems for studying the genetics of cancer initiation and progression. To develop a cross-species comparison strategy for identifying CRC causative gene or genomic alterations, we performed array comparative genomic hybridization (aCGH) to investigate copy number abnormalities (CNAs), one of the most prominent lesion types reportedfor human CRCs, in 10 spontaneously occurring canine CRCs. The results revealed for the first time a strong degree of genetic homology between sporadic canine and human CRCs. First, we saw that between 5% and 22% of the canine genome was amplified/deleted in these tumors, and that, reminiscent of human CRCs, the total altered sequences directly correlated to the tumor’s progression stage, origin,and likely microsatellite instability status. Second, when mapping the identified CNAs onto syntenic regions of the human genome, we noted that the canine orthologs of genes participating in known human CRC pathways were recurrently disrupted, indicating that these pathways might be altered in the canine CRCs as well. Last, we observed a significant overlapping of CNAs between human and caninetumors, and tumors from the two species were clustered according to the tumor subtypes but not the species. Significantly, compared with the shared CNAs, we found that species-specific (especially human-specific) CNAs localize to evolutionarily unstable regions that harbor more segmental duplications and interspecies genomic rearrangement breakpoints. These findings indicate that CNAs recurrent betweenhuman and dog CRCs may have a higher probability of being cancer-causative, compared with CNAs found in one species only. [Supplemental material is available online at http:/ /www.genome.org. The aCGH data have been submitted to the NCBI Gene Expression Omnibus (http:/ /www.ncbi.nlm.nih.gov/geo/) under accession no. GSE19318.]
Cancer is a disease of the genome, and genomic instability is a...