Abstract A028: Incidental detection of age-related somatic genomic alterations in blood samples from dogs with and without cancer
Authors: Tsui Dana W.Y. , O'Kell Allison L. , Cohen Todd A. , Lytle Katherine M. , Kruglyak Kristina M. , Marshall Maggie A. , Ruiz-Perez Carlos A. , Tynan John A. , Hicks Susan C. , Rafalko Jill M. , Grosu Daniel S. , Chibuk Jason , Chorny Ilya , McCleary-Wheeler Angela L. , Flory Andi 
Published: January 2023

Abstract
The concept of age-related somatic alterations in the blood or bone marrow of humans, commonly referred to as clonal hematopoiesis of indeterminate potential (CHIP) or age-related clonal hematopoiesis (ARCH), has been well characterized. In humans, these abnormalities tend to be associated with advanced age, often exhibit consistent signal over time, and typically involve recurrent locations in the genome. Though these somatic alterations may be associated with an increased risk of cancer, they do not originate from the tumor when cancer is concurrently present in the body. This study describes early findings that suggest similar age-related somatic alterations may also be present in dogs. Recently, next-generation sequencing-based liquid biopsy testing was developed for cancer detection in dogs. The clinical validation of this test involved 1,100 cancer-diagnosed and presumably cancer-free client-owned dogs. The test has also been performed commercially in thousands of additional dogs since 2021. This recent ability to test large numbers of dogs using liquid biopsy affords an unprecedented opportunity to study the genomic profiles of a broad population of canine subjects. Blood samples from over three thousand dogs ranging in age from 1 to &gt;15 years were used in this analysis. Cell-free DNA (cfDNA) was extracted from the plasma, and genomic DNA (gDNA) was extracted from the white blood cells present in the buffy coat. Both cfDNA and gDNA were analyzed using next-generation sequencing to identify somatic genomic alterations. In a subset of patients, tumor tissue was also available for evaluation. Recurrent variants (e.g., involving CFA6 and CFA25, among others) were identified in the gDNA of a small fraction of patients. These findings occurred more commonly in older dogs and were typically persistent in gDNA across subsequent timepoints (when available) with no significant change in signal over time. When a clinical cancer evaluation was pursued, the majority of dogs with these findings had no evidence of cancer. For those in which cancer was identified, and tumor tissue was available for testing, the genomic profiles of the tumor tissue and gDNA were uncorrelated in almost all cases, suggesting the concomitant presence of age-related somatic alterations was incidental to the patient’s cancer. Additionally, regardless of whether cancer was present in the patient, the variants detected in gDNA were typically not encountered in cfDNA. These findings may be early evidence for the existence of age-related somatic alterations in dogs that potentially resemble the phenomenon of CHIP/ARCH previously observed in humans. Additional studies are ongoing to determine if these incidental findings may represent a risk factor for cancer development in dogs.
Citation Format: Dana W.Y. Tsui, Allison L. O'Kell, Todd A. Cohen, Katherine M. Lytle, Kristina M. Kruglyak, Maggie A. Marshall, Carlos A. Ruiz-Perez, John A. Tynan, Susan C. Hicks, Jill M. Rafalko, Daniel S. Grosu, Jason Chibuk, Ilya Chorny, Angela L. McCleary-Wheeler, Andi Flory. Incidental detection of age-related somatic genomic alterations in blood samples from dogs with and without cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A028.