Canine mammary tumor risk is associated with polymorphisms in <i>RAD51</i> and <i>STK11</i> genes

Canadas, Ana; Santos, Marta; Nogueira, Augusto; Assis, Joana; Gomes, Mónica; Lemos, Carolina; Medeiros, Rui; Dias‐Pereira, Patrícia

doi:10.1177/1040638718789231

Cited by 18 publications

(21 citation statements)

References 23 publications

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“…Three missense variants were identified, STK11 c.C109T (p.P37S), STK11 c.A286G (p.M96V), and STK11 c.T293C (p.F98S), all of which appear to play a role in CMT risk. Our findings suggest that STK11 is a CMT susceptibility gene, corroborating a similar claim in a recent publication by Canadas et al [68]. Canadas and colleagues suggested that the minor allele (T) of rs22928814, which lies within an intron of STK11, was associated with an increased risk of CMT.…”

Section: Discussionsupporting

confidence: 92%

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Huskey

Goebel

Lloveras-Fuentes

et al. 2020

Canine Genet Epidemiol

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Background: Although, in general, cancer is considered a multifactorial disease, clustering of particular cancers in pedigrees suggests a genetic predisposition and could explain why some dog breeds appear to have an increased risk of certain cancers. To our knowledge, there have been no published reports of whole genome sequencing to investigate inherited canine mammary tumor (CMT) risk, and with little known about CMT genetic susceptibility, we carried out whole genome sequencing on 14 purebred dogs diagnosed with mammary tumors from four breedspecific pedigrees. Following sequencing, each dog's data was processed through a bioinformatics pipeline. This initial report highlights variants in orthologs of human breast cancer susceptibility genes. Results: The overall whole genome and exome coverage averages were 26.0X and 25.6X, respectively, with 96.1% of the genome and 96.7% of the exome covered at least 10X. Of the average 7.9 million variants per dog, initial analyses involved surveying variants in orthologs of human breast cancer susceptibility genes, BRCA1, BRCA2, CDH1, PTEN, STK11, and TP53, and identified 19 unique coding variants that were validated through PCR and Sanger sequencing. Statistical analyses identified variants in BRCA2 and STK11 that appear to be associated with CMT, and breed-specific analyses revealed the breeds at the highest risk. Several additional BRCA2 variants showed trends toward significance, but have conflicting interpretations of pathogenicity, and correspond to variants of unknown significance in humans, which require further investigation. Variants in other genes were noted but did not appear to be associated with disease.

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Section: Discussionsupporting

confidence: 92%

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Huskey

Goebel

Lloveras-Fuentes

et al. 2020

Canine Genet Epidemiol

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“…Some ESR1 genetic differences were described between different dog breeds known to be at high and at low risk of mammary tumor development; furthermore, an association between ESR1 variation and the susceptibility to mammary tumors was described in a cohort of English Springer Spaniels [31,32]. However, in a recent investigation, our group could not confirm a relationship between ESR1 genetic profile and the risk of development of mammary tumors [33]. On the other hand, genetic variations in canine COMT gene (which encodes catechol-O-methyltransferase, an enzyme involved in estrogens metabolism through inactivation of carcinogenic catechol estrogens) has not been proved to influence susceptibility to canine mammary tumors.…”

Section: Introductioncontrasting

confidence: 56%

Estrogen receptors genotypes and canine mammary neoplasia

et al. 2019

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Background Estrogens are essential for the development and proper function of several hormone-dependent organs. There are, however, several lines of evidence associating estrogens with mammary carcinogenesis. A marked individual genetic variability concerning estrogens biosynthesis, metabolism and mechanism of action was recognized and associated with human breast cancer susceptibility, clinical features and progression. Although some genetic variations in canine ESR1 gene were reported, their influence in clinicopathological features and progression of canine mammary tumors has not been fully evaluated. This study aims to assess the influence of SNPs in ESR1 gene (rs397512133, rs397510462, rs851327560, rs397510612, rs852887655, rs852684753 and rs852398698) in canine mammary tumors characteristics and progression. A group of 155 non-neutered bitches with mammary tumors was included in the study. Follow-up information was assessed 24 months after surgery. Results Genetic profiles associated with a later onset of mammary tumors and less aggressive clinicopathological features, namely smaller tumor size (≤ 3 cm) with extensive tubular differentiation and low canine-adapted prognostic index (vet-NPI), were identified in this study. Conclusions Our data suggest that the ESR1 genetic profile may help on the decision regarding the selection of individual tailored preventive measures against canine mammary tumors development, such as early neutering.

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“…Each tumour was evaluated for the mode of growth and classified as either expansive, when it was delimited with a capsule; infiltrative, when not delimited by a capsule, but without signs of vascular invasion or lymph node metastasis; and invasive in the presence of vascular invasion or lymph node metastases. In cases of dogs with multiple malignant tumours, a reference lesion was assigned for the statistical study, as previously reported …”

Section: Methodsmentioning

confidence: 99%

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Canadas

Santos

Medeiros

et al. 2019

Vet Comparative Oncology

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E-cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E-cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case-control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non-infiltrative, noninvasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features. K E Y W O R D S canine mammary tumour, CDH1 gene, E-cadherin, risk, SNP

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Canine mammary tumor risk is associated with polymorphisms in RAD51 and STK11 genes

Cited by 18 publications

References 23 publications

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Whole genome sequencing for the investigation of canine mammary tumor inheritance - an initial assessment of high-risk breast cancer genes reveal BRCA2 and STK11 variants potentially associated with risk in purebred dogs

Estrogen receptors genotypes and canine mammary neoplasia

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

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