Single Nucleotide Polymorphisms Influence Histological Type and Grade of Canine Malignant Mammary Tumours

Histological examination of canine mammary tumours is mandatory for determining the histological type and grade of the lesions, features that provide relevant information regarding the biological behaviour of the disease. Different histological classification systems and grading methods have been used to characterize canine mammary tumours. In this study, the relationship between the genetic profile of 87 female dogs (i.e. single nucleotide polymorphisms [SNPs] in genes known to be involved in mammary carcinogenesis) and the histological type and grade of malignant mammary tumours was assessed. The results demonstrated a significant relationship between genetic variation in genes RAD51, BRCA2, CHEK2, HER2, CDH1, COMT and PGR and these morphological features of the mammary lesions. Specifically, SNPs in RAD51 (rs23623251 and rs23642734), CHEK2 (rs397511718), HER2 (rs24537329) and PGR (rs8875007) were related to aggressive histotypes, with moderate to high histological grade. In contrast, SNPs in BRCA2 (rs23255542), HER2 (rs24537331), CDH1 (rs852280880 and rs850805755) and COMT (rs851328636, rs853133060 and rs85346495) were associated with tumour histotypes of good prognosis and of low histological grade. These data provide preliminary evidence for a genotypic-phenotypic correlation in canine mammary tumours, highlighting the mechanisms of their genesis, development and progression.