Investigation of Cell-Free DNA in Dogs with Hepatocellular Carcinoma
Principal Investigator: Jessica Hayward
Co-PI: Kelly Hume
DESCRIPTION (provided by applicant):
Hepatocellular carcinoma (HCC) is the most common liver cancer seen in dogs. Surgical resection of the tumor is the standard treatment of care, but its use is limited by tumor location and morphological subtype. Although HCC is considered slow-growing, it is often not detected until the later stages of disease. Levels of the blood liver enzymes alanine aminotransferase (ALT) and alkaline phosphatase (ALP) provide an indication of liver damage, and alpha-fetoprotein (AFP) levels may be a result of liver cancer, but none of these are specific to a diagnosis of HCC.
Cell-free DNA (cfDNA) is short DNA fragments circulating in the blood that originate from cells undergoing apoptosis and necrosis. Cell-free DNA has been shown to be a promising biomarker for early detection and prognosis in cancers of humans and, more recently, of dogs. As far as we are aware, there has not been a longitudinal study of cell-free DNA in canine HCC patients.
The main aim of this proposed research is to investigate and characterize the cfDNA circulating in dogs with HCC over time. We have three specific objectives: 1) to compare the amount of circulating cfDNA with clinical manifestation for longitudinal samples from individual patients, 2) to perform whole-genome sequencing on paired tumor-normal samples from each individual to identify shared HCC-specific mutations, and 3) to perform whole-genome sequencing on cell-free DNA samples to determine if the shared mutations in aim 2 are present in the cell-free DNA. The broader long-term aim is to develop a non-invasive blood sampling technique for earlier detection of this cancer in dogs, therefore resulting in better outcomes and improved health for our canine companions.