Ocular Squamous Cell Carcinoma, SCC

 

Gene: DDB2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease. Both parents of an affected animal must be carriers of at least one copy of the mutation. Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, DDB2 gene; c.1013 C>T, p.(T338M), exon7

Medical system: Ocular

Breeds: Appaloosa, American Paint Horse, Haflinger, Belgian, Connemara pony

Age of onset of symptoms: On average, before 9 years of age

Ocular squamous cell carcinoma (SCC) is the most common ocular tumor in the horse and is the second most common type of tumor in the horse overall after the sarcoid tumor. Risk factors for SCC include a genetic mutation of the DDB2 gene and exposure to UV light. The DDB2 gene is responsible for recognizing and repairing UV-induced damage to DNA. The mutation in the DDB2 gene prevents recognition and repair of damaged DNA which can predispose the individual to cancer.  SCC can lead to visual impairment and is a locally invasive tumor that can take over the globe of the eye, bony orbit and the nervous system. Surgical excision is considered to be curative, however rates of recurrence without adjunct therapy can be high. Metastasis is uncommon. DNA testing is available to identify carriers (M/N) and higher risk (M/M) individuals. This information can be used in breeding decisions to reduce the rate of affected individuals and to implement management strategies in higher risk (M/M) to prevent or delay the onset of cancer.

 

References:

OMIA link: [0735-9796]

Chen L, Bellone RR, Wang Y, et al. (2021) A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma. DNA Repair (Amst) 97:103022.  [pubmed/33276309]

Knickelbein KE, Lassaline ME, Singer-Berk M, et al. (2020) A Missense Mutation in Damage-Specific DNA Binding Protein 2 Is a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Belgian Horses. Equine Vet J. 52(1):34-40. [pubmed/30903710]

Singer-Berk M, Knickelbein KE, Vig S, et al. (2018) Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses. Anim Genet. 49(5):457-460. [pubmed/29999543]

Bellone RR, Liu J, Petersen JL, et al. (2017) A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses. Int J Cancer. 141(2):342-353. [pubmed/28425625]

Lassaline M, Cranford TL, Latimer CA, et al. (2015) Limbal Squamous Cell Carcinoma in Haflinger Horses.  Vet Ophthalmol. 18(5):404-8. [pubmed/25312447]

 

Contributed by: Emily Morgan, Class of 2020, Faculty of Veterinary Medicine, University of Montreal.