Liquid biopsy can detect BRCA2 gene variants in female dogs with mammary neoplasia

Abstract

Mammary tumours (MT) are one of the most prevalent malignancies in female dogs and women. Currently, molecular analyzes have shown that each tumour type presents its own genetic signature. In this context, liquid biopsy allows a comprehensive genetic characterisation of the tumour, enabling early diagnosis and personalised treatment of patients. In women, deleterious mutations inherited in BRCA2 gene are associated with an increased risk of breast cancer, resistance to therapies and worse prognosis. In female dogs, there are many divergent data on the involvement of BRCA2 gene with mammary carcinogenesis and what its pathogenic potential is. Therefore, the objective was to identify BRCA2 gene variants in 20 plasma DNA samples, from 10 newly diagnosed dogs with mammary cancer (RD), five control (CTR) and five mastectomized patients. Eleven single nucleotide polymorphisms (SNPs) were detected, most of them in the exon 11 and two indels (deletion/insertion) in the BRCA2 gene. However, there was no statistically significant difference in the SNPs/indels detected between the groups. In addition, only one SNP (p.T1425P) and one deletion (p.L2307del) were considered deleterious using in silico computational models. Interestingly, most common variants were present in the plasma of all groups, except for the Ile2614Thr, Ile2614Val, Thr1425Pro and p.L2307del variants. Thus, we observed that SNPs are common in the BRCA2 gene of female dogs with MT, with a similar condition identified in women with breast cancer. Liquid biopsy approach in dogs with MT is useful for genetic and therapeutic proposals.

A Highly Conserved Region in BRCA2 Suppresses the RAD51-Interaction Activity of BRC Repeats

“…LC687405, and 5788G>A (synonymous); accession No. LC687406) [ 10 , 15 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. According to the SIFT scores, K801Q (2609A>C), I1110M (3538T>G), T1425P (4481A>C), and I2226M (6886A>G) were intolerant.…”

>b<Detecção de células tumorais circulantes (CTCs) por isolamento baseado em tamanho e reação em cadeia da polimerase via transcriptase- reversa em tempo real (RT-qPCR) em cães com melanoma oral>/b<

“…A identificação do ctDNA dentro do cfDNA pela detecção de mutações e rearranjos vem sendo estudada mais recentemente. Grande foco é dado ao estudo do ctDNA em pacientes com carcinomas, principalmente os mamários e uroteliais (BECK et al, 2013;BEFFAGNA et al, 2017;DE OLIVEIRA et al, 2022;LEE et al, 2019;TAGAWA et al, 2020), mas mutações e rearranjos cromossomais específicos para linfoma, sarcoma histiocítico e até mesmo no melanoma oral canino já foram detectadas no plasma de cães, demonstrando potencial para o diagnóstico e na avaliação da doença residual mínima (PROUTEAU; ANDRÉ, 2019). A quantidade de ctDNA poderia diferenciar lesões benignas de lesões malignas, visto que resultados significativamente distintos foram observados entre lesões esplênicas benignas e malignas (FAVARO et al, 2022).…”

“…A biópsia líquida tem sido muito estudada em oncologia humana, porém ela é pouco abordada em medicina veterinária . Muitos dos estudos já realizados focam em detecção de ctDNA (BECK et al, 2013;BEFFAGNA et al, 2017;DE OLIVEIRA et al, 2022;LEE et al, 2019;MOCHIZUKI et al, 2015;PROUTEAU et al, 2021;TAGAWA et al, 2019TAGAWA et al, , 2020.…”