Characterizing Circulating Nucleosomes in the Plasma of Dogs with Hemangiosarcoma

Wilson-Robles, Heather; Terrell, Jason; Kelly, Theresa K.; Miller, Tasha; Bygott, Thomas; Bougoussa, Mhammed; Jarvis, Jill

doi:10.21203/rs.3.rs-310756/v1

Cited by 3 publications

(9 citation statements)

References 32 publications

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“…Nucleosome levels were evaluated in plasma samples from patients with seven of the most common canine cancers. The dogs with the most frequent elevations in plasma nucleosome concentrations were dogs with hemangiosarcoma and lymphoma, consistent with previous publications [20,21]. Other cases with frequent elevations in plasma nucleosome concentrations include those with histiocytic sarcoma and oral malignant melanoma.…”

Section: Discussionsupporting

confidence: 89%

“…For a specificity of 100% the cut off for the healthy range was set at 67.5 ng/mL (nucleosome range for all healthy dogs was 6.33-67.42 ng/mL). Neither age, neuter status, gender or size had an effect on nucleosome concentrations in either cohort of dogs [21] .…”

Section: Resultsmentioning

confidence: 76%

“…Detailed evaluations of plasma nucleosome concentrations in dogs with lymphoma and hemangiosarcoma by stage, location or phenotype have been described elsewhere [20,21]. For the cases with melanoma there were two main groups.…”

Section: Resultsmentioning

confidence: 99%

“…Histiocytic sarcomas involving the bone had the lowest median plasma nucleosome concentrations (Fig. 6) [21]. Stage and size of the tumor was not available for comparison.…”

Section: Resultsmentioning

confidence: 99%

“…Few studies exist defining the plasma nucleosome compartment in canine cancer. Recently, our group published data demonstrating increased plasma nucleosome concentrations in dogs with lymphoma and hemangiosarcoma [19][20][21]. In these studies, increased plasma nucleosome concentrations were found in the majority of cases with cancer, even in early stages of disease.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs

et al. 2022

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Background Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs. Results The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors. Conclusions A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

“…Histiocytic sarcomas involving the bone had the lowest median plasma nucleosome concentrations (Fig. 6) [21]. Stage and size of the tumor was not available for comparison.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs

et al. 2022

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Monitoring plasma nucleosome concentrations to measure disease response and progression in dogs with hematopoietic malignancies

Wilson-Robles

Warry

Miller

et al. 2023

Preprint

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Background: Hematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound and baseline blood work to monitor these patients for treatment response and remission. Circulating biomarkers, such as prostate specific antigen or carcinoembryonic antigen, can be useful tools for monitoring treatment response and remission status in human cancer patients. To date, there has a been a lack of useful circulating biomarkers available to veterinary oncology patients. Methods: Circulating plasma nucleosome concentrations were evaluated at diagnosis, throughout treatment and during remission monitoring for 40 dogs with lymphoma, acute myelogenous leukemia and multiple myeloma. Additionally, C-reactive protein and thymidine kinase-1 levels were recorded. Results: Plasma nucleosome concentrations were significantly higher at diagnosis and progressive disease than they were when dogs were in remission. All but two dogs had plasma nucleosome concentrations that returned to the low range during treatment. These two dogs had the shortest progression free and overall survival times. Dogs with the highest plasma nucleosome concentrations had a significantly shorter first progression free survival than dogs with lower plasma nucleosome concentrations at diagnosis. Plasma nucleosome concentrations correlated better with disease response and progression than either thymidine kinase or C reactive protein. Conclusions: Plasma nucleosome concentrations can be a useful tool for treatment monitoring and disease progression in dogs with hematopoietic malignancies.

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Characterizing circulating nucleosomes in the plasma of dogs with lymphoma

et al. 2021

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Background Nucleosomes consist of DNA wrapped around a histone octamer core like beads on a string so that DNA can be condensed as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death where chromatin is fragmentated and released as mononucleosomes into the blood. The Nu.Q™ H3.1 assay measures total nucleosome concentration in plasma of humans and has been used to detect and identify cancer even at early stages. The objectives of this study were to determine if nucleosome levels could be used to distinguish between healthy dogs and dogs with various stages of lymphoma (LSA) using the Nu.Q™ H3.1 assay. A total of 126 dogs diagnosed with LSA and 134 healthy controls were recruited for this study. Plasma was collected from each dog and stored in K2-EDTA tubes. The LSA patient samples were recruited from TAMU or purchased from various biobanks. All control cases were recruited from TAMU. Results Dogs with LSA had an approximately 7-fold increase in their plasma nucleosome concentrations compared to controls (AUC 87.8%). Nucleosome concentrations increased with cancer stage and dogs with B cell lymphomas had significantly higher nucleosome concentrations than dogs with T cell lymphomas. Conclusions The Nu.Q™ H3.1 assay was able to reliably detect elevated nucleosome concentrations in the plasma of dogs with LSA. Furthermore, it appears that nucleosomes are useful for differentiating cancer from healthy individuals in canines.

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Characterizing Circulating Nucleosomes in the Plasma of Dogs with Hemangiosarcoma

Cited by 3 publications

References 32 publications

Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs

Evaluation of plasma nucleosome concentrations in dogs with a variety of common cancers and in healthy dogs

Monitoring plasma nucleosome concentrations to measure disease response and progression in dogs with hematopoietic malignancies

Characterizing circulating nucleosomes in the plasma of dogs with lymphoma

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