Abstract 1612: Comparative oncology analysis of canine cancer by tumor and liquid biopsy testing for biomarker and therapeutic discovery in humans and dogs
Authors: Chorny Ilya , Kruglyak Kristina M. , Tynan John A. , Hernandez Gilberto E. , Nakashe Prachi , Hicks Susan , Motalli-Pepio Rita , McLennan Lisa , Holtvoigt Lauren E. , Rafalko Jill M. , Chibuk Jason , McCleary-Wheeler Angela L. , Flory Andi , Grosu Daniel S. , Tsui Dana W. 
Published: June 2022

Abstract
Human and canine cancers share a high level of homology. Characterizing their respective genomic landscapes can expand the knowledge base of comparative oncology and support biomarker discovery and therapeutic development for the benefit of both species. Genomic profiling via tumor biopsy infers risk to the patient in both human and veterinary medicine and is often complicated by tumor heterogeneity. Blood-based liquid biopsy has been shown to open new opportunities to profile the cancer genome noninvasively in both species. The goal of this study was to benchmark the occurrence of homologous genomic variants in a variety of canine cancers that have a counterpart in humans, including lymphoma (B-cell and T-cell), soft-tissue sarcoma, osteosarcoma, and melanoma, among others, utilizing tumor and liquid biopsy profiling. The study was performed in a prospective cohort of over 300 client-owned dogs that received a confirmed cancer diagnosis either at the time of enrollment or after sample collection. A blood sample was collected prior to biopsy or surgical resection of the tumor to evaluate the use of liquid biopsy to noninvasively profile the cancer genome. Tumor tissue samples were collected at the time of surgical resection. In a subset of the subjects, blood samples were collected 3 to 30 days following surgical removal of the tumor, and longitudinally during cancer therapy and monitoring. The Cancer Gene Census (CGC) and COSMIC databases were interrogated, and a high degree of homology (&gt;90%) between human and canine oncogenes and tumor suppressor genes was observed. A custom panel was designed encompassing 95 of the top 100 human DNA single nucleotide variants from COSMIC that had a canine orthologue, and targeted sequencing was performed on all tissue and blood samples. A large number of these variants—many of which are actionable in human cancer— were detected in the tumor samples and pre-surgical plasma samples. In some patients, tumor-derived variants were detected in the post-surgical plasma that confirmed the presence of residual disease after surgery. As disease progressed, an increase in the variant allele fraction (VAF) of the tumor-derived mutations was observed and tracked with the patient’s clinical course. Additionally, the presence of variants that may be targetable by human cancer drugs were identified in a subset of patients. These findings demonstrate the potential of liquid biopsy to characterize the genomic landscape of canine cancers at diagnosis and throughout treatment, similar to observations reported in human cancers. This builds the foundation for comparative oncology to translate the knowledge of precision medicine between humans and dogs, to facilitate biomarker discovery, and to track emergence of potential actionable biomarkers in various therapeutic contexts to the benefit of both species.
Citation Format: Ilya Chorny, Kristina M. Kruglyak, John A. Tynan, Gilberto E. Hernandez, Prachi Nakashe, Susan Hicks, Rita Motalli-Pepio, Lisa McLennan, Lauren E. Holtvoigt, Jill M. Rafalko, Jason Chibuk, Angela L. McCleary-Wheeler, Andi Flory, Daniel S. Grosu, Dana W. Tsui. Comparative oncology analysis of canine cancer by tumor and liquid biopsy testing for biomarker and therapeutic discovery in humans and dogs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1612.