Genetic variants of BRCA1 and BRCA2 genes in cats with mammary gland carcinoma
| Autor: | Tereza Cristina da Silva, Bruno Cogliati, Juliana Mariotti Guerra, Isabel Veloso Alves Pereira, Felisbina L. Queiroga, Verônica Mollica Govoni |
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| Rok vydání: | 2021 |
| Předmět: |
Somatic cell
Genes BRCA2 Mammary gland Breast Neoplasms Mammary Neoplasms Animal Triple Negative Breast Neoplasms Biology Cat Diseases Genetic analysis Germline Exon medicine Carcinoma Animals Humans Neoplasm Genetic Predisposition to Disease skin and connective tissue diseases BRCA2 Protein CATS General Veterinary BRCA1 Protein medicine.disease NEOPLASIAS MAMÁRIAS medicine.anatomical_structure Mutation Cats Cancer research Female |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Mammary tumours are the first and third most incident neoplasm in women and cats, respectively. Approximately 85% of feline mammary gland tumours are malignant and aggressive, especially the triple-negative and HER-2+ molecular subtypes. Triple-negative basal-like feline mammary carcinomas (FMCs) are considered suitable models due to the clinical and morphological similarities with human basal-like triple-negative breast cancer (TNBC). In women, TNBC has a poor prognosis and is often associated with mutations in the tumour suppressor genes BRCA1 and BRCA2. In light of this, the aim of the present investigation was to screen somatic and germline variants of BRCA1 and BRCA2 in nine female cats bearing FMCs. Matched whole blood and FMC samples were obtained for genetic analysis. Additional tumour samples were obtained for histopathological and immunohistochemical evaluation. Genomic DNA was isolated and 27 exonic regions of BRCA1 and BRCA2 genes were amplified and screened by next-generation sequencing. A somatic variant with high functional impact was found in exon 11 of BRCA2 at a frequency of 4.34% in one FMC-bearing cat. Four germline variants with moderate impact were detected in three of the nine FMC-bearing cats and were restricted to exon 9 of BRCA1. It is concluded that the germline genetic variants found in one-third of FMC-bearing animals might be associated with a higher risk of hereditary mammary carcinogenesis. |
| Databáze: | OpenAIRE |
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