OMIA:000735-9796 : Ocular squamous cell carcinoma in Equus caballus (horse) |
In other species: domestic cat , taurine cattle , goat , sheep
Categories: Neoplasm
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 278740 (trait)
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Disease-related: yes
Key variant known: yes
Year key variant first reported: 2017
Cross-species summary: Malignant new growth of squamous epithelial cells in the eye. Also called eye cancer.
Species-specific symbol: SCC
Species-specific description: “Squamous cell carcinoma (SCC) is the most common cancer of the equine eye, and is second to equine sarcoid as the most common tumor of the horse overall. . . . The Haflinger breed, developed in Austria and Northern Italy during the late 19th century, appears to be among those breeds overrepresented for this disease” (Bellone et al., 2017) {contributed by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019}
Inheritance: Bellone et al. (2017) reported pedigree data consistent with autosomal recessive inheritance, based on examination of the pedigrees for 43 affected and 24 unaffected horses. {revised version contributed by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019}
Mapping: A GWAS conducted by Bellone et al. (2017) on using 12 cases and 11 controls, each genotyped with the EquineSNP70 BeadChip yielding 41,743 informative SNPs, identified a 1.5Mb candidate region on chromosome EC12. {revised version based on a contribution by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019}
Markers: By "sequencing the most physiologically relevant gene from [the candidate region on EC12, namely] damage specific DNA binding protein 2 (DDB2)", Bellone et al. (2017) "identified a missense mutation (c.1013 C > T p.Thr338Met) that was strongly [but not completely] associated with limbal SCC". Singer-Berk et al. (2018) reported "that the genetic risk [for the above variant] is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses". Knickelbein et al. (2019) reported the same variant homozygous in a Rocky Mountain Horse stallion. Knickelbein et al. (2020) reported that the same variant "is a risk factor for ocular SCC in Belgian horses". The extent to which this variant is an incomplete risk factor in this breed is indicated by the genotypic distribution of this variant among affected Belgian horses, namely 76% homozygous, 8% heterozygous, and 16% lacking the variant. Chen et al. (2020) "provide direct functional evidence indicating that the T338M mutant indeed is a loss-of-function allele that abolishes UV-DDB recognition of damaged DNA."
Clinical features: “Squamous cell carcinoma (SCC) is a slow-growing malignant neoplasia of the skin, mucous membranes and mucocutaneous junctions. It is the most common tumor of the eye and adnexa in the horse. Most commonly, the nictitating membrane, nasal canthus, limbus and eyelids are affected. Untreated ocular SCC may invade local soft tissues, the bony orbit, sinuses and brain and less commonly, it may metastasize to the regional lymph nodes, salivary glands and thorax. Limbal involvement can quickly lead to visual impairment and destruction of the globe” (Kaps et al., 2005). {contributed by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019}
Prevalence: For breeds in which SCC has been reported, the variant allele frequencies reported by Bellone et al. (2017) are 0.25 for Haflingers, 0.21 for Belgians, 0.20 for Rocky Mountain Horses, 0.07 for Percherons, 0.02 for Appaloosas, and zero for Arabian, Clydesdale, Dutch Warmblood, Hanoverian, Oldenburg, Paint Horse, Quarter Horse, Shire, and Thoroughbred. The breeds with zero variant frequency (but in which SCC has been reported) are indicative of the extent to which this variant is incompletely associated with SCC. Knickelbein et al. (2019) reported the frequency of the same variant in the Rocky Mountain breed to be 0.2. {much of the above information was contributed by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019}
Breeds:
Appaloosa (Horse) (VBO_0000904),
Belgian Draft (Horse) (VBO_0000915),
Connemara Pony (Horse) (VBO_0000937),
Haflinger (Horse) (VBO_0000978),
Rocky Mountain, United States of America (Horse) (VBO_0011836),
Welsh Pony (Horse) (VBO_0001091).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).
Associated gene:
Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
---|---|---|---|---|---|---|
DDB2 | damage-specific DNA binding protein 2 | Equus caballus | 12 | NC_009155.3 (11691531..11729191) | DDB2 | Homologene, Ensembl , NCBI gene |
Variants
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
167 | Belgian Draft (Horse) Connemara Pony (Horse) Haflinger (Horse) Rocky Mountain, United States of America (Bighorn sheep) Welsh Pony (Horse) | Ocular squamous cell carcinoma | DDB2 | missense | Naturally occurring variant | EquCab3.0 | 12 | NC_009155.3:g.11726667C>T | XM_023654000.1:c.1013C>T | XP_023509768.1:p.(T338M) | The EquCab2 coordinates, obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool, are g.11608667, c.1013C>T and p.T338M | rs1139682898 | 2017 | 28425625 | The EquCab3 g. coordinates were provided by by Meredith O’Connell, working under the guidance of Professor Ernie Bailey, 5 March 2019. Breed information updated based on PMID: 38600096 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000735-9796: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
References
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2024 | Chow, L., Flaherty, E., Pezzanite, L., Williams, M., Dow, S., Wotman, K. : |
Impact of equine ocular surface squamous neoplasia on interactions between ocular transcriptome and microbiome. Vet Sci 11:167, 2024. Pubmed reference: 38668434. DOI: 10.3390/vetsci11040167. | |
Durward-Akhurst, S.A., Marlowe, J.L., Schaefer, R.J., Springer, K., Grantham, B., Carey, W.K., Bellone, R.R., Mickelson, J.R., McCue, M.E. : | |
Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 14:8396, 2024. Pubmed reference: 38600096. DOI: 10.1038/s41598-024-57872-8. | |
Hollis, A.R. : | |
Squamous cell carcinomas in horses: An update of the aetiopathogenesis and treatment options. Vet Clin North Am Equine Pract , 2024. Pubmed reference: 39168748. DOI: 10.1016/j.cveq.2024.07.007. | |
2023 | Schäfer, J., May, A., Wittenberg, J., Hahn, K., Graubner, C., Gerber, V., Drögemüller, C., Unger, L. : |
[DDB2-associated incidence of squamous cell carcinoma in Haflingers: risk minimization by genotyping]. Schweiz Arch Tierheilkd 165:707-715, 2023. Pubmed reference: 37905572. DOI: 10.17236/sat00409. | |
2021 | Chen, L., Bellone, R.R., Wang, Y., Singer-Berk, M., Sugasawa, K., Ford, J.M., Artandi, S.E. : |
A novel DDB2 mutation causes defective recognition of UV-induced DNA damages and prevalent equine squamous cell carcinoma. DNA Repair (Amst) 97:103022, 2021. Pubmed reference: 33276309. DOI: 10.1016/j.dnarep.2020.103022. | |
2020 | Crausaz, M., Launois, T., Smith-Fleming, K., McCoy, A.M., Knickelbein, K.E., Bellone, R.R. : |
DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds. Genes (Basel) 11:1460, 2020. Pubmed reference: 33291392. DOI: 10.3390/genes11121460. | |
Knickelbein, K.E., Lassaline, M.E., Singer-Berk, M., Reilly, C.M., Clode, A.B., Famula, T.R., Miller Michau, T., Bellone, R.R., Knickelbein, K.E., Lassaline, M.E., Singer-Berk, M., Reilly, C.M., Clode, A.B., Famula, T.R., Michau, T.M., Bellone, R.R. : | |
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 52:34-40, 2020. Pubmed reference: 30903710. DOI: 10.1111/evj.13116. | |
2019 | Knickelbein, K.E., Lassaline, M.E., Bellone, R.R. : |
Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and investigation of genetic contribution. Vet Ophthalmol 22:201-205, 2019. Pubmed reference: 30238589. DOI: 10.1111/vop.12612. | |
2018 | Singer-Berk, M., Knickelbein, K.E., Vig, S., Liu, J., Bentley, E., Nunnery, C., Reilly, C., Dwyer, A., Drögemüller, C., Unger, L., Gerber, V., Lassaline, M., Bellone, R.R. : |
Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses. Anim Genet 49:457-460, 2018. Pubmed reference: 29999543. DOI: 10.1111/age.12695. | |
2017 | Bellone, R.R. : |
Genetic testing as a tool to identify horses with or at risk for ocular disorders. Vet Clin North Am Equine Pract 33:627-645, 2017. Pubmed reference: 29103563. DOI: 10.1016/j.cveq.2017.08.005. | |
Bellone, R.R., Liu, J., Petersen, J.L., Mack, M., Singer-Berk, M., Drögemüller, C., Malvick, J., Wallner, B., Brem, G., Penedo, M.C., Lassaline, M. : | |
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 141:342-353, 2017. Pubmed reference: 28425625. DOI: 10.1002/ijc.30744. | |
2015 | Lassaline, M., Cranford, T.L., Latimer, C.A., Bellone, R.R. : |
Limbal squamous cell carcinoma in Haflinger horses. Vet Ophthalmol 18:404-8, 2015. Pubmed reference: 25312447. DOI: 10.1111/vop.12229. | |
2005 | Kaps, S., Richter, M., Philipp, M., Bart, M., Eule, C., Spiess, B.M. : |
Primary invasive ocular squamous cell carcinoma in a horse. Vet Ophthalmol 8:193-7, 2005. Pubmed reference: 15910373. DOI: 10.1111/j.1463-5224.2005.00358.x. | |
1996 | Vanderwoerdt, A., Gilger, B.C., Wilkie, D.A. : |
Penetrating keratoplasty for treatment of recurrent squamous cell carcinoma of the cornea in a horse Journal of the American Veterinary Medical Association 208:1692 ff., 1996. | |
1991 | Dugan, S.J., Curtis, C.R., Roberts, S.M., Severin, G.A. : |
Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses. J Am Vet Med Assoc 198:251-6, 1991. Pubmed reference: 2004985. | |
Dugan, S.J., Roberts, S.M., Curtis, C.R., Severin, G.A. : | |
Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978-1988). J Am Vet Med Assoc 198:298-303, 1991. Pubmed reference: 2004996. | |
1987 | Schwink, K. : |
Factors influencing morbidity and outcome of equine ocular squamous cell carcinoma. Equine Vet J 19:198-200, 1987. Pubmed reference: 3608956. | |
1978 | Eversole, T.G., Lavach, J.D. : |
Primary ocular squamous cell carcinoma with metastasis in a horse. Vet Med Small Anim Clin 73:287-90, 1978. Pubmed reference: 247797. | |
1976 | Strafuss, A.C. : |
Squamous cell carcinoma in horses. J Am Vet Med Assoc 168:61-2, 1976. Pubmed reference: 1245449. |
Edit History
- Created by Frank Nicholas on 06 Sep 2005
- Changed by Frank Nicholas on 11 May 2017
- Changed by Frank Nicholas on 26 Mar 2019
- Changed by Frank Nicholas on 28 Mar 2019
- Changed by Frank Nicholas on 23 Jan 2020
- Changed by Frank Nicholas on 28 Jan 2020
- Changed by Imke Tammen2 on 11 Dec 2020
- Changed by Frank Nicholas on 24 Jan 2022
- Changed by Frank Nicholas on 31 Jul 2022
- Changed by Frank Nicholas on 27 Apr 2023
- Changed by Imke Tammen2 on 28 Apr 2023
- Changed by Imke Tammen2 on 04 Jun 2024