Quantitative analysis of the BRAF V595E mutation in plasma cell-free DNA from dogs with urothelial carcinoma

Circulating tumor DNA (ctDNA), which carries tumor-specific mutations, is an emerging candidate biomarker for malignancies and for monitoring disease status in various human tumors. Recently, BRAF V595E mutation has been reported in 80% of dogs with urothelial carcinoma. This study investigates the...

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Bibliographic Details
Published in:PloS one 2020-04, Vol.15 (4), p.e0232365-e0232365
Main Authors: Tagawa, Michihito, Tambo, Naomi, Maezawa, Masaki, Tomihari, Mizuki, Watanabe, Ken-Ichi, Inokuma, Hisashi, Miyahara, Kazuro
Format: Article
Language:English
Subjects:
Alleles
Biology and Life Sciences
Biomarkers
Biopsy
Bladder cancer
Cancer
Cancer genetics
Cancer therapies
Carcinoma
Deoxyribonucleic acid
Development and progression
Diseases
DNA
Dogs
EDTA
Gene expression
Gene mutation
Genes
Genetic aspects
Health services
Medical treatment
Medicine and Health Sciences
Monitoring
Mutation
Nucleic acids
Plasma
Polymerase chain reaction
Quantitative analysis
Real time
Telemedicine
Time
Tumors
Ultrasonic imaging
Urothelial carcinoma
Veterinary medicine
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Summary:Circulating tumor DNA (ctDNA), which carries tumor-specific mutations, is an emerging candidate biomarker for malignancies and for monitoring disease status in various human tumors. Recently, BRAF V595E mutation has been reported in 80% of dogs with urothelial carcinoma. This study investigates the BRAF V595E allele concentration in circulating cell-free DNA (cfDNA) and assesses the clinical significance of BRAF-mutated ctDNA levels in canines with urothelial carcinoma. A total of 15 dogs with urothelial carcinoma were included. cfDNA concentration was measured using a real-time polymerase chain reaction (PCR) of the LINE-1 gene. To measure the concentration of the mutated BRAF gene in cfDNA, allele-specific real-time PCR with a locked nucleic acid probe was performed. BRAF mutations were detected in 11 (73%) of the 15 tested tumor samples. BRAF-mutated ctDNA concentrations were significantly higher in dogs with the BRAF mutation (14.05 ± 13.51 ng/ml) than in wild-type dogs (0.21 ± 0.41 ng/ml) (p = 0.031). The amount of BRAF-mutated ctDNA in plasma increased with disease progression and responded to treatment. Our results show that BRAF-mutated ctDNA can be detected using allele-specific real-time PCR in plasma samples of canines with urothelial carcinoma with the BRAF V595E mutation. This ctDNA analysis may be a potentially useful tool for monitoring the progression of urothelial carcinoma and its response to treatment.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0232365