Molecular Homology and Difference between Spontaneous Canine Mammary Cancer and Human Breast Cancer

Abstract

Spontaneously occurring canine mammary cancer (MC) represents an excellent model of human breast cancer but is greatly understudied. To better utilize this valuable resource, we performed whole genome sequencing, whole exome sequencing, RNA-seq and/or high density arrays on 12 canine MC cases, including 7 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, appear to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated, and are abnormally enriched with active histone modification H4-acetylation while 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.

Comparative oncology: Integrating human and veterinary medicine

“…Canine simple carcinomas histologically mimic typical human breast carcinomas and could serve as a cancer model for basal-like tumours (Liu et al, 2014). These features support the use of canine mammary tumours as a spontaneous tumour model with diverse translational value to human mammary carcinogenesis.…”

Nucleosome positioning changes during human embryonic stem cell differentiation

“…SNPs, compared to the hg18 genome, were identified using SAMtools 66 and GATK. 67 CNVs were identified as described, [68][69][70] Then, we identified genomic regions that are amplified, considered as sites with higher nucleosome occupancy, or deleted, deemed sites with lower nucleosome occupancy, as described. [68][69][70] Next, we examined sequence mutations in these regions as described above.…”

Aflatoxins ingestion and canine mammary tumors: There is an association?

“…Study of mammary tumors in female dogs is a good model for clinical, pathological, diagnostic and prognostic investigations of human mammary tumors (Schneider, 1970;Liu et al, 2014). Breast cancer is defined as a multifactorial disease and is the most frequent neoplasm in female dogs, while in women, it is the main cause of death throughout the world, with a high rate of malignancy in both species (Morrison, 1998;Jemal et al, 2011;INCA, 2013).…”

“…Breast cancer is defined as a multifactorial disease and is the most frequent neoplasm in female dogs, while in women, it is the main cause of death throughout the world, with a high rate of malignancy in both species (Morrison, 1998;Jemal et al, 2011;INCA, 2013). In both species, mammary tumors arise from genomic aberrations and also, from epigenomic alterations (Liu et al, 2014). Risk factors such as age, hormonal influence, nutrition and exogenous progesterone administration can modulate neoplasm growth in female dogs (Perez Alenza et al, 2000), whereas in women these tumors were associated with few births, early menarche, late menopause, alcoholism and smoking (INCA, 2013).…”