Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses

2018 ◽  
Vol 49 (5) ◽  
pp. 457-460 ◽  
Author(s):  
M. Singer-Berk ◽  
K. E. Knickelbein ◽  
S. Vig ◽  
J. Liu ◽  
E. Bentley ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Risk ◽  
Nictitating Membrane

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

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1460
Author(s):  
Margo Crausaz ◽  
Thomas Launois ◽  
Kathryn Smith-Fleming ◽  
Annette M. McCoy ◽  
Kelly E. Knickelbein ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Risk ◽  
Mate Selection ◽  
Missense Variant ◽  
Genetic Risk Factor ◽  
Dna Testing ◽  
Gene Damage

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.

scholarly journals A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses

2017 ◽  
Vol 141 (2) ◽  
pp. 342-353 ◽  
Author(s):  
Rebecca R. Bellone ◽  
Jiayin Liu ◽  
Jessica L. Petersen ◽  
Maura Mack ◽  
Moriel Singer-Berk ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Risk Factor ◽  
Dna Binding ◽  
Cell Carcinoma ◽  
Missense Mutation ◽  
Squamous Cell ◽  
Genetic Risk ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Genetic Risk Factor

Skeletal metastasis from a squamous cell carcinoma of the nictitating membrane in a Haflinger horse

2019 ◽  
Author(s):  
M. de Preux ◽  
C. Gurtner ◽  
I. Klebic ◽  
M. A. Waschk ◽  
C. Drögemüller ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Skeletal Metastasis ◽  
Nictitating Membrane

scholarly journals Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Moriel H. Singer-Berk ◽  
Kelly E. Knickelbein ◽  
Zachary T. Lounsberry ◽  
Margo Crausaz ◽  
Savanna Vig ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Risk ◽  
High Throughput Sequencing ◽  
Risk Allele ◽  
Dna Binding Protein ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Better Than

Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC cases were genotyped for the DDB2 variant and associations were investigated. Horses with urogenital SCC that were heterozygous for the DDB2 risk allele were identified in the Appaloosa breed, but a significant association between the DDB2 variant and SCC occurring at any location in this breed was not detected. The risk allele was not identified in Arabians, and no Percherons were homozygous for the risk allele. High-throughput sequencing data from six Haflingers were analyzed to ascertain if any other variant from the previously associated 483 kb locus on ECA12 was more concordant with the SCC phenotype than the DDB2 variant. Sixty polymorphisms were prioritized for evaluation, and no other variant from this locus explained the genetic risk better than the DDB2 allele (P=3.39×10−17, n=118). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds.

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