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Frequent Alteration of the Tumor Suppressor Gene APC in Sporadic Canine Colorectal Tumors

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https://ir.library.oregonstate.edu/concern/articles/cf95jc262

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  • Sporadic canine colorectal cancers (CRCs) should make excellent models for studying the corresponding human cancers. To molecularly characterize canine CRC, we investigated exonic sequence mutations of adenomatous polyposis coli (APC), the best known tumor suppressor gene of human CRC, in 23 sporadic canine colorectal tumors, including 8 adenomas and 15 adenocarcinomas, via exon-resequencing analysis. As a comparison, we also performed the same sequencing analysis on 10 other genes, either located at human 5q22 (the same locus as APC) or 18q21 (also frequently altered in human CRC), or known to play a role in human carcinogenesis. We noted that APC was the most significantly mutated gene in both canine adenomas and adenocarcinomas among the 11 genes examined. Significantly, we detected large deletions of ≥10 bases, many clustered near the mutation cluster region, as well as single or two base deletions in ~70% canine tumors of both subtypes. These observations indicate that like in the human, APC is also frequently altered in sporadic colorectal tumors in the dog and its alteration is an early event in canine colorectal tumorigenesis. Our study provides further evidence demonstrating the molecular similarity in pathogenesis between sporadic human and canine CRCs. This work, along with our previous copy number abnormality study, supports that sporadic canine CRCs are valid models of human CRCs at the molecular level.
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  • Youmans L, Taylor C, Shin E, Harrell A, Ellis AE, Séguin B, et al. (2012) Frequent Alteration of the Tumor Suppressor Gene APC in Sporadic Canine Colorectal Tumors. PLoS ONE 7(12): e50813. https://doi.org/10.1371/journal.pone.0050813
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  • 7
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  • 12
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  • This work was funded by the American Cancer Society and the Georgia Cancer Coalition (PI: Zhao); the National Science Foundation of China (31160021 and 31270131), Science and Technological Project of Yunnan Province (2011CI) and Foundation for Key Teacher of Yunnan University (PI: Ji); the NCIP50 CA128613 (PI: Dr. Dong M. Shin) and GM085354 (PI: Dr. Stephen Dalton). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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