OMIA 000735-9796 : Ocular squamous cell carcinoma in Equus caballus

In other species: cattle , sheep , goat , domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 278740

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: 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}

Molecular basis: 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; Vet Ophth) reported the same variant homozygous in a Rocky Mountain Horse stallion.

Knickelbein et al. (2019; EVJ) 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.

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; Vet Ophth) 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, Belgian, Haflinger, Percheron, Rocky Mountain.

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

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Belgian Haflinger Percheron Ocular squamous cell carcinoma DDB2 missense EquCab3 12 g.11726667C>T 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

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.
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.
Knickelbein, K.E., Lassaline, M.E., Singer-Berk, M., Reilly, C.M., Clode, A.B., Famula, T.R., Miller Michau, T., 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 :, 2019. Pubmed reference: 30903710. DOI: 10.1111/evj.13116.
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 :, 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 :, 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.

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