Presença da mutação do gene BRCA1 em cadelas com tumores mamários malignos
Presence of BRCA1 gene mutation in bitches with malignant mammary tumors
Acta sci. vet. (Impr.); 49 (), 2021
Publication year: 2021
Mammary tumors (MTs) in bitches are similar to breast cancers in women. Thus, they can be used as a
model for human breast cancer and findings can be extrapolated for use in human medicine. BRCA1 is a tumor suppressor
gene. When the gene has a mutation, it cannot repair damaged DNA, which causes genetic instability and tumorigenesis.
Therefore, we aimed to study the frequency of single nucleotide polymorphisms (SNPs) in the BRCA1 gene that are associated with distinct histological types of malignant MT in bitches. The study population consisted of 91 bitches, including a control group of 6 animals
with healthy mammary glands and 85 animals with MTs. All animals underwent a presurgery evaluation consisting of
a questionnaire administered to the person responsible for the animal, a physical examination, collection of peripheral
blood for hematological and serum biochemistry evaluations, an electrocardiogram, and a preanesthesia evaluation. In
addition, distant metastasis was studied via chest radiography and abdominal ultrasound. After evaluations were complete,
the animals that could undergo surgery were administered general anesthesia and underwent a mastectomy or mammary
gland sample collection. Histopathological examination and molecular analysis were performed to identify mutations in
the BRCA1 gene. Histopathological examinations found 10 different types of malignant tumors in 36 sick animals. Tumor
samples plus samples from the 6 control animals were subjected to DNA extraction, polymerase chain reaction (PCR)
analysis, and genetic sequencing. The tumor with the highest incidence (33.33%) was a complex carcinoma, followed by
carcinoma in mixed tumor (13.88), tubular carcinoma (13.88) and carcinosarcoma (13.88). Molecular analysis revealed
3 different SNP points in 5 samples (4006G>A, 3619A>G, and 3761C>T). The allelic variant 4006G>A (1/36) resulted
in the alteration of the amino acid valine by isoleucine (V1336 I). The mutation 3619A>G (2/36) inserted the amino acid
alanine instead of threonine (T1207 A). The mutation 3761C>T (2/36) led to the alteration of the amino acid serine by
phenylalanine (S1254 F), a mutation for which there are no published reports. The histological types that showed BRCA1
mutations were complex carcinoma (1/5), carcinoma in mixed tumor (1/5), papillary carcinoma (1/5) and tubular carcinoma
(2/5). Software analysis identified the new SNP (nucleotide 3761) in BRCA1 and 2 point mutations in nucleotides 4006
and 3619 and responsible for genetic instability. The development of breast cancer is caused by many endogenous and exogenous factors. The results of our
study show that these factors have a greater presence in female, mixed breed, uncastrated, and older dogs, confirming the
data in the veterinary literature. In the present study, we found different histological types of malignant breast tumors with
mutations in the BRCA1 gene, as other authors have reported. However, we also found the mutation 3761C>T, which, to
the best of our knowledge, has not been reported in the literature. This shows the need for studies in veterinary medicine
that assess mutations in the BRCA1 gene and the most common histological types. In conclusion, SNPs in the BRCA1
gene cause genetic instability, resulting in additional mutations that lead to the development of breast tumors. They are
point mutations that affect transcription, resulting in truncated proteins. These proteins may have a loss of function, leading to carcinogenesis.(AU)