Impact of preanalytical factors on liquid biopsy in the canine cancer model

While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact of preanalytical factors such as the timing and anatomical location of blood draw is not well understood.

To address this gap, we leveraged pet dogs with spontaneous cancer as a model system for liquid biopsy of plasma cell-free DNA (cfDNA), as their compressed disease timeline facilitates rapid diagnostic benchmarking. We examined key cfDNA metrics, including DNA concentration in plasma, as well as tumor fraction and fragment size ratio derived from ultra low pass whole genome sequencing.

We show that liquid biopsy metrics in dogs are consistent with reported human metrics. The tumor content of samples is slightly higher when blood is obtained from a central vein closer to the tumor. Metrics also differ between lymphoma and non-hematopoietic cancers, supporting cancer-type-specific interpretation. Disease status tracks with liquid biopsy findings over the course of treatment over both short (hours to days) and long (weeks to months) time frames, and trends of increased tumor fraction and other metrics are observed prior to clinical relapse in dogs with lymphoma and osteosarcoma.

Together, these data support the utility of pet dogs with cancer as a relevant system for advancing liquid biopsy platforms.