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

Abstract

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.

Review of Molecular Technologies for Investigating Canine Cancer

“…Q™ H3.1 Assay’ is designed for the detection of levels of histone H3.1-containing cfNucleosomes in human serum and has also been used to show that serum from canines with lymphoma contains a 7-fold-increased nucleosome level in their plasma relative to healthy control dogs [ 30 ]. Using this assay, a recent study quantified and characterised nucleosome concentrations in both healthy dogs ( n = 134) and those dogs with various cancer types ( n = 528) and found that tumours of haematopoietic origin were most likely to result in increased nucleosome concentrations in the plasma, whereas local tumours such as soft tissue sarcomas were the least likely to have this result [ 31 ]. However, it is important to note that the levels of nucleosomes can only be used for cancer detection in an otherwise clinically healthy dog, as other studies have shown that concentrations of nucleosomes are significantly higher in dogs under certain conditions relative to healthy controls, such as dogs with sepsis, with acute gastroenteropathies or following trauma [ 32 , 33 , 34 ].…”

New Perspectives on the Importance of Cell-Free DNA Biology

“…While cfDNA research on non-human animals is not as developed as in humans, there is increasing interest in the role of cfDNA as a biomarker as well as a tool to study pathophysiology in animals, especially companion animals. For example, several studies indicate the potential of implementing cfDNA tests in veterinary clinics for the minimally-invasive diagnosis and monitoring of cancer in dogs [ 471 , 472 , 473 , 474 , 475 , 476 , 477 ]. Furthermore, cfDNA may also serve as a potential marker of gastric dilatation–volvulus (GDV) [ 478 ] and immune-mediated hemolytic anemia (IMHA) [ 479 ], tissue injury [ 480 ], and sepsis [ 481 , 482 , 483 ] in dogs.…”

Comparison of Nucleosome, Ferritin and LDH Levels in Blood with Clinical Response before and after Electrochemotherapy Combined with IL-12 Gene Electrotransfer for the Treatment of Mast Cell Tumours in Dogs

“…Biomarkers that could predict the response to treatment of different tumours with ECT or the combination of ECT with IL-12 GET have not yet been investigated in veterinary oncology. Nucleosome and ferritin concentrations and the LDH activity in blood have been shown to be valuable diagnostic biomarkers for various malignancies in animals [26][27][28][29][30][31][32][33][34][35].…”