DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds.

Margo Crausaz,Annette M Mccoy,Kathryn Smith-Fleming,Kelly E Knickelbein,Thomas Launois,Rebecca R Bellone

doi:10.3390/genes11121460

Abstract

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye. A missense variant within the gene damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) was previously identified as a causal recessive genetic risk factor for the development of ocular SCC within Haflingers, Belgian Draft horses, and Rocky Mountain Horses, but not in the Appaloosa or Arabian breeds. This study aimed to evaluate three cases of ocular SCC in additional breeds and determine if DNA testing for the DDB2 variant in warmblood horses and Connemara ponies is warranted. Histopathology confirmed ocular SCC in all three cases and DNA testing confirmed each horse was homozygous for the DDB2 risk factor. The DDB2 risk allele frequency was estimated to be 0.0043 for Holsteiners (N = 115), 0.014 for Belgian Warmbloods (N = 71), and 0.22 for Connemara Ponies (N = 86). Taken together these data support using DNA testing for DDB2 in Connemara Ponies to assist in mate selection and clinical management. Given the low observed allele frequencies in both the Holsteiner and Belgian Warmblood breeds and that the case under investigation was a warmblood cross-bred, evaluating additional SCC affected warmbloods is warranted to fully determine the importance of DDB2 genotyping as a risk factor in warmblood breeds.

Highlights

Squamous cell carcinoma (SCC) is the most common cancer impacting the equine eye and follows equine sarcoids as the second most common equine cancer overall [1,2,3]
Investigation of the genetic risk for ocular SCC in Haflingers identified a recessive allele in damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) [4,10]
The aim of this study is to report the occurrence of the DDB2 c.1013C>T variant in additional cases and to identify the allele frequency of this variant in larger sample cohorts from the Holsteiner, Belgian Warmblood, and Connemara Pony breeds

Summary

Introduction

Squamous cell carcinoma (SCC) is the most common cancer impacting the equine eye and follows equine sarcoids as the second most common equine cancer overall [1,2,3]. These tumors primarily arise from the limbus, nictitating membrane, and upper or lower eyelids and prognosis varies with location, progression, and treatment. Investigation of the genetic risk for ocular SCC in Haflingers identified a recessive allele in damage-specific DNA binding protein 2

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Conclusion