Quantification of plasma cell-free DNA levels in dogs with various tumors

Tagawa, Michihito; Shimbo, Genya; Inokuma, Hisashi; Miyahara, Koshiro

doi:10.1177/1040638719880245

Cited by 35 publications

(56 citation statements)

References 32 publications

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“…As in human, cfDNA concentration in dogs is correlated with the severity of the disease and prognosis 16,17,20,53 . Consistently with previous studies, we found that dogs with multicentric lymphoma had significantly higher concentration of total cfDNA than healthy dogs, dogs with non-cancerous diseases and dogs with other cancers 20,51 . Our cfDNA concentrations were in agreement with those of previous studies, although results were highly variable in terms of median cfDNA concentrations, ranging from 4 to 583ng/ml in healthy dogs for example.…”

Section: Discussionsupporting

confidence: 92%

“…cfDNA is an attractive biomarker in human medicine and particularly in oncology. Thus, it has also been evaluated in different canine diseases 16,17,19,20,[50][51][52][53] . As in human, cfDNA concentration in dogs is correlated with the severity of the disease and prognosis 16,17,20,53 .…”

Section: Discussionmentioning

confidence: 99%

“…Our cfDNA concentrations were in agreement with those of previous studies, although results were highly variable in terms of median cfDNA concentrations, ranging from 4 to 583ng/ml in healthy dogs for example. In those studies, authors used different extraction kits and quantification methods, 16,20,51,53 that could in part explain this interstudy variability. Thus, this high variability of cfDNA concentration in healthy dogs limits its interest as a global biomarker for cancer diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Prouteau

Denis

Fornel³

et al. 2020

Preprint

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Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology and may be informative in cancer-affected dogs. By performing ddPCR or PARR methods, we detected tumor-specific point mutations, copy number alterations and chromosomal rearrangements in the plasma of cancer-affected dogs. It allowed the detection of ctDNA in 2/8 (25%) oral malignant melanoma cases, 12/13 (92.3%) lymphoma cases and 21/23 (91.3%) histiocytic sarcoma (HS) cases. The value of ctDNA to diagnose HS was explored in 133 dogs including 49 with HS. In this cohort, screening recurrent PTPN11 mutations in plasma had a specificity of 98.8%, and a sensitivity between 42.8-77% according to HS clinical presentation, being higher in internal forms, especially with pulmonary location. Regarding lymphoma, the follow-up of four dogs showed that the minimal residual disease detection by targeting lymphoma-specific antigen receptor rearrangement in the plasma was concordant with the clinical evaluation. Moreover, ctDNA analysis appeared interesting to assess treatment response and to predict relapse.This study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a relevant biomarker for diagnosis and clinical follow-up. With a growing interest in integrating natural canine tumors to explore new therapies, this biomarker appears promising in comparative oncology research.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Prouteau

Denis

Fornel³

et al. 2020

Preprint

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“…Elevated concentrations of cfDNA have been reported in dogs with cancer, however, this is the first time, to the authors' knowledge, that elevated nucleosome concentrations have specifically been reported in dogs with cancer (13,32,33).…”

Section: Discussionmentioning

confidence: 64%

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

Wilson-Robles

Miller

Jarvis

et al. 2020

Preprint

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AbstractIntroductionNucleosomes consist of small fragments of DNA wrapped around a histone octamer core. Diseases such as cancer or inflammation lead to cell death, which causes fragmentation and release of nucleosomes into the blood. The Nu.Q™ technology measures circulating nucleosome levels and exploits the different compositions of cancer derived nucleosomes in blood to detect and identify cancer even at early stages. The objectives of this study are to identify the optimal sample type for the Nu.Q™ H3.1 assay and to determine if it can accurately detect nucleosomes in the blood of healthy canines as well as those with cancer.Materials and MethodsBlood samples from healthy canine volunteers as well as dogs newly diagnosed with lymphoma were used. The blood was processed at a variety of times under a variety of conditions to determine the most reliable sample type and conditions, and to develop an appropriate processing strategy to ensure reliably accurate results.ResultsNucleosomes could be detected using a variety of sample collection and processing protocols. Nucleosome signals were highest in EDTA plasma and serum samples and most consistent in plasma. Samples should be processed within an hour of collection. Experiments showed that samples were able to withstand several freeze thaw cycles. Processing time and tcollection tube type did affect nucleosome detection levels. Finally, significantly elevated concentrations of nucleosomes were seen in a small cohort of dogs that had been newly diagnosed with lymphoma.ConclusionsWhen samples are collected and processed appropriately, the Nu.Q™ platform can reliably detect nucleosomes in the plasma of dogs. Further testing is underway to validate and optimize the Nu.Q™ platform for veterinary use.

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“…The plasma cfDNA concentration was measured using a quantitative real-time PCR (qPCR) reaction of long interspersed nuclear element-1 (LINE-1), as previously described [14]. The results of this assay were used for the normalization of DNA volume to be used in the qPCR for the BRAF mutation.…”

Section: Quantification Of Cfdna Using the Line-1 Genementioning

confidence: 99%

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

et al. 2020

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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 cellfree 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.

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Quantification of plasma cell-free DNA levels in dogs with various tumors

Cited by 35 publications

References 32 publications

Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Interest of circulating tumor DNA as a biomarker for canine cancers: illustration in histiocytic sarcoma, oral malignant melanoma and multicentric lymphoma

Evaluation of nucleosome concentrations in healthy dogs and dogs with cancer

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

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