title: Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Lydia
authors.initials: L
authors.lastname: Youmans
authors.forename: Cynthia
authors.initials: C
authors.lastname: Taylor
authors.forename: Edwin
authors.initials: E
authors.lastname: Shin
authors.forename: Adrienne
authors.initials: A
authors.lastname: Harrell
authors.forename: Angela E
authors.initials: AE
authors.lastname: Ellis
authors.forename: Bernard
authors.initials: B
authors.lastname: Séguin
authors.forename: Xinglai
authors.initials: X
authors.lastname: Ji
authors.forename: Shaying
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D009154:Mutation
chemical_list: D025601:Adenomatous Polyposis Coli Protein