Abstract
BackgroundNucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes. Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood. The Nu.Q™ platform measures circulating nucleosomes in the blood of humans that result from disease and has been used to detect and identify cancer even at early stages. The objectives of this study are to quantify and better characterize nucleosomes in dogs with various stages of hemangiosarcoma (HSA) using this ELISA-based assay.Samples from 77 dogs with a confirmed diagnosis of hemangiosarcoma and 134 healthy controls were utilized for this study. The HSA samples were recruited from the Texas A&M University Small Animal Clinic (TAMU-SAC) or purchased from biobanks. All control samples were recruited from the TAMU-SAC.ResultsDogs with hemangiosarcoma had a 6.6-fold increase in their median plasma nucleosome concentrations compared to controls (AUC 92.9 %). Elevated nucleosome concentrations were seen at all stages of disease and nucleosome concentrations increased with the stage of the disease.ConclusionsPlasma nucleosome concentrations are a reliable way to differentiate dogs with hemangiosarcoma from healthy dogs. Further testing is underway to better characterize cancer associated HSA circulating nucleosomes and optimize future diagnostics for canine HSA detection.
Highlights
Liquid biopsy (LB) techniques refer to the minimally invasive approach of sampling tumor specific biomarkers in the blood of diseased patients [1]
LB has been most studied in the field of oncology; literature exists on the use of LB for the prognostication of inflammation, sepsis and trauma in humans and dogs [2,3,4,5]
The purpose of this study was to determine if dogs with hemangiosarcoma (HSA), an aggressive mesenchymal tumor derived from malignant endothelial cell precursors, demonstrated elevated concentrations of plasma nucleosomes when compared to healthy dogs [17]
Summary
Liquid biopsy (LB) techniques refer to the minimally invasive approach of sampling tumor specific biomarkers in the blood of diseased patients [1]. LB techniques are used to identify intact circulating tumor cells, extracellular nucleic acids such as cell free DNA (cfDNA), messenger RNA (mRNA), microRNA (miRNA), extracellular vesicles (exosomes), The detection of cfDNA in the blood of cancer patients is a rapidly emerging field in cancer diagnostics [6] These techniques allow for the minimally invasive detection of cancer DNA as an adjunct or even as an alternative to standard biopsy approaches. Nucleosomes consist of DNA wrapped around a histone octamer core like thread on a spool to condense DNA as chromatin into chromosomes Diseases such as cancer or inflammation lead to cell death, chromatin fragmentation and release of nucleosomes into the blood.
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