title: Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer.
abstract: Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia.
authors.forename: Deli
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia.
authors.forename: Huan
authors.initials: H
authors.lastname: Xiong
authors.affiliation: College of Veterinary Medicine, University of Georgia, Athens, Georgia.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Ellis
authors.affiliation: College of Veterinary Medicine, University of Georgia, Athens, Georgia.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Northrup
authors.affiliation: School of Veterinary Medicine, University of California, Davis, California.
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Rodriguez
authors.affiliation: The Winship Cancer Center, Emory School of Medicine, Atlanta, Georgia.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: O'Regan
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dalton
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Bioinformatics, University of Georgia, Athens, Georgia. szhao@bmb.uga.edu.
authors.forename: Shaying
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009693:Nucleic Acid Hybridization
chemical_list: D014408:Biomarkers, Tumor
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