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Genetic variants of BRCA1 and BRCA2 genes in cats with mammary gland carcinoma
Veterinary and Comparative Oncology ( IF 2.1 ) Pub Date : 2021-02-12 , DOI: 10.1111/vco.12685
Verônica Mollica Govoni 1 , Tereza Cristina Da Silva 1 , Juliana Mariotti Guerra 1 , Isabel Veloso Alves Pereira 1 , Felisbina Luisa Queiroga 2, 3 , Bruno Cogliati 1
Affiliation  

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.

中文翻译:

BRCA1和BRCA2基因在患有乳腺癌的猫中的遗传变异

乳腺肿瘤分别是女性和猫发病率第一和第三的肿瘤。大约 85% 的猫乳腺肿瘤是恶性和侵袭性的,尤其是三阴性和 HER-2 +分子亚型。由于与人类基底样三阴性乳腺癌 (TNBC) 的临床和形态相似性,三阴性基底样猫乳腺癌 (FMC) 被认为是合适的模型。在女性中,TNBC 预后较差,通常与肿瘤抑制基因BRCA1BRCA2的突变有关。鉴于此,本研究的目的是在九只携带 FMC 的雌性猫中筛选BRCA1BRCA2的体细胞和种系变体. 获得匹配的全血和 FMC 样本用于遗传分析。获得额外的肿瘤样本用于组织病理学和免疫组织化学评估。分离基因组 DNA,通过二代测序扩增和筛选BRCA1BRCA2基因的27 个外显子区域。在一只携带 FMC 的猫中,在BRCA2 的外显子 11 中发现了具有高功能影响的体细胞变异,频率为 4.34%。在九只携带 FMC 的猫中的三只中检测到四种具有中等影响的种系变异,并且仅限于BRCA1 的外显子 9. 结论是,在三分之一携带 FMC 的动物中发现的种系遗传变异可能与较高的遗传性乳腺癌发生风险有关。
更新日期:2021-02-12
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