Canine cutaneous histiocytoma: A model for human pediatric disease?

Abstract

This study investigates alterations at the level of the genome and at level of gene expression in dogs with Canine Cutaneous Histiocytoma (CCH). CCH is a benign tumor originating from Langerhans cells (LC), remarkably like pediatric LC Histiocytoma. While CCH is highly prevalent in young dogs, it spontaneously regresses within 2–3 mo, providing a unique opportunity to study immune-mediated tumor control. Unlike many canine tumors, CCH has no clear breed or sex predisposition. To unravel the biology of this disease, we conducted a retrospective study using data from DNATech Laboratory, analyzing 359 cases from 2020 to 2022 from Portugal. Incidence rates were calculated based on the 2023 registered dog population. The mean age was 3.7 years, with nearly 50% of cases occurring in dogs under 2 years old. The sample included 41 breeds, with mixed-breed dogs (25.9%), French Bulldogs (24.0%), and Labradors (7.0%) being the most common. From these, 60% of cases were from the cities of Lisbon and Setúbal and therefore for robustness remaining analysis were performed in these cases. The overall incidence rate in the Lisbon and Setúbal regions was 4.0 cases per 10,000 dogs. Male French Bulldogs had the highest risk and the highest relative risk when compared with mixed breed dogs (IR = 37.8, RR = 13.1), followed by male Boxers (IR = 27.4, RR = 9.5). From breeds that are not brachycephalic Labradors had the highest risk (IR = 4.8, RR = 1.6). Given the differences, at risk level between breeds, the effect of breed should be further investigated at the genomic level. To uncover novel biological insights regarding the development of CCH we performed whole-genome sequencing 30x and transcriptome sequencing (RNA-seq). This study included samples from animals with (n = 8) and without CCH (n = 2) from French Bulldogs, Labradors, and mixed breeds. DNA and RNA were extracted from Formalin-fixed, paraffin-embedded samples using AllPrep® DNA/RNA FFPE, Qiagen. The results demonstrate significant differences between samples with and without CCH, and between breeds, which can provide crucial insights into immune responses against LC tumors, with potential implications for human disease.