OMIA:001441-9615 : Osteosarcoma in Canis lupus familiaris (dog) |
In other species: domestic cat , Chinese water deer
Categories: Neoplasm
Single-gene trait/disorder: yes
Disease-related: yes
Key variant known: no
Species-specific symbol: OSA
Inheritance: In addition to somatic mutations leading to osteosarcoma, it is likely that regulatory, non-coding variants underlie the increased risk for cancer development in some breeds. Momen et al. (2021) estimated that the heritability of osteosarcoma in the Irish Wolfhound was 0.65 and Letko et al. (2021) estimated heritability (h2SNP) to be 20.6% in Leonberger dogs based on a breed prevalence of 20%.
Mapping:
Letko et al. (2021) "performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases with a median age of 8.1 [3.1-13.5] years and 365 controls older than eight years. This analysis revealed significant associations at the CDKN2A/B gene locus on canine chromosome 11 ...".
Lucas et al. (2024) conducted a comparative oncology analysis which included mapping information about osteosarcoma risk in dogs generated by Karlsson et al. (2013) to identify a novel human osteosarcoma risk allele near GRB10, a growth inhibitor that suppresses activated receptor tyrosine kinases including IGF1R, PDGFRB, and EGFR.
Molecular basis: Sarver et al. (2023): "A hallmark of osteosarcoma in both human and canine tumors is somatic fragmentation and rearrangement of chromosome structure which leads to recurrent increases and decreases in DNA copy number. The PTEN gene has been implicated as an important tumor suppressor in osteosarcoma ... . PTEN function is abrogated by different mechanisms in canine and human osteosarcoma tumors leading to uncontrolled cell cycling. Somatic loss of this canine specific syntenic region may help explain why the canine genome appears to be uniquely susceptible to osteosarcoma."
Breeds:
Doberman Pinscher (Dog) (VBO_0200442),
German Shepherd Dog (Dog) (VBO_0200577),
Great Dane (Dog) (VBO_0200623),
Greyhound (Dog) (VBO_0200638),
Irish Setter (Dog) (VBO_0200702),
Irish Wolfhound (Dog) (VBO_0200706),
Leonberger (Dog) (VBO_0200819),
Rottweiler (Dog) (VBO_0201143),
Saint Bernard (Dog) (VBO_0201160),
Scottish Deerhound (Dog) (VBO_0201195).
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).
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2025). OMIA:001441-9615: 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.
| 2025 | Hong, Y., Baik, H., Lee, J., Oh, W.S., Ryu, J., Baek, S.J. : |
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| Power, K., Leandri, R., Federico, G., De Vico, G., Leonardi, L. : | |
| Ferritinophagy: a possible new iron-related metabolic target in canine osteoblastic osteosarcoma. Front Vet Sci 12:1546872, 2025. Pubmed reference: 40196812. DOI: 10.3389/fvets.2025.1546872. | |
| 2024 | Ammons, D.T., Hopkins, L.S., Cronise, K.E., Kurihara, J., Regan, D.P., Dow, S. : |
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| Brot, S., Cobb, J., Alibhai, A.A., Jackson-Oxley, J., Haque, M., Patke, R., Harris, A.E., Woodcock, C.L., Lothion-Roy, J., Varun, D., Thompson, R., Gomes, C., Kubale, V., Dunning, M.D., Jeyapalan, J.N., Mongan, N.P., Rutland, C.S. : | |
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| Bryan, J.N. : | |
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| Leonardi, L., Manuali, E., Bufalari, A., Porcellato, I. : | |
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| Lucas, S.E., Yang, T., Wimberly, C.E., Parmar, K.V., Hansen, H.M., de Smith, A.J., Morimoto, L.M., Metayer, C., Ostrom, Q.T., Eward, W.C., Graves, L.A., Wagner, L.M., Wiemels, J.L., Spector, L.G., Walsh, K.M. : | |
| Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations. Cancer Epidemiol 92:102599, 2024. Pubmed reference: 38871555. DOI: 10.1016/j.canep.2024.102599. | |
| Ludwig, L., Edson, M., Treleaven, H., Viloria-Petit, A.M., Mutsaers, A.J., Moorehead, R., Foster, R.A., Ali, A., Wood, R.D., Wood, G.A. : | |
| Plasma microRNA signatures predict prognosis in canine osteosarcoma patients. PLoS One 19:e0311104, 2024. Pubmed reference: 39739708. DOI: 10.1371/journal.pone.0311104. | |
| Shank, A.M.M., Snook, E., Cavender, K., McCoy, J., Sorensen, N., Siegrist, B., Tabb, B. : | |
| Special AT-rich sequence-binding protein 2 immunohistochemistry in the diagnosis of osteosarcoma in dogs. J Comp Pathol 215:S0021-9975(24)00304-9:14-29, 2024. Pubmed reference: 39368249. DOI: 10.1016/j.jcpa.2024.09.001. | |
| Silver, K.I., Mannheimer, J.D., Saba, C., Hendricks, W.P.D., Wang, G., Day, K., Warrier, M., Beck, J.A., Mazcko, C., LeBlanc, A.K. : | |
| Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma. Res Sq , 2024. Pubmed reference: 38659878. DOI: 10.21203/rs.3.rs-4223759/v1. | |
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| Proteomic analyses reveal the role of alpha-2-macroglobulin in canine osteosarcoma cell migration. Int J Mol Sci 25:3989, 2024. Pubmed reference: 38612805. DOI: 10.3390/ijms25073989. | |
| 2023 | Ammons, D.T., Harris, R.A., Hopkins, L.S., Kurihara, J., Weishaar, K., Dow, S. : |
| A single-cell RNA sequencing atlas of circulating leukocytes from healthy and osteosarcoma affected dogs. Front Immunol 14:1162700, 2023. Pubmed reference: 37275879. DOI: 10.3389/fimmu.2023.1162700. | |
| Hayward, J.J., Todhunter, R.J. : | |
| Common orthopedic traits and screening for breeding programs. Vet Clin North Am Small Anim Pract 53:1013-1029, 2023. Pubmed reference: 37225647. DOI: 10.1016/j.cvsm.2023.04.004. | |
| Klosowski, M., Haines, L., Alfino, L., McMellen, A., Leibowitz, M., Regan, D. : | |
| Naturally occurring canine sarcomas: Bridging the gap from mouse models to human patients through cross-disciplinary research partnerships. Front Oncol 13:1130215, 2023. Pubmed reference: 37035209. DOI: 10.3389/fonc.2023.1130215. | |
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| Transcriptional profiling of canine osteosarcoma identifies prognostic gene expression signatures with translational value for humans. Commun Biol 6:856, 2023. Pubmed reference: 37591946. DOI: 10.1038/s42003-023-05208-z. | |
| Nance, R.L., Wang, X., Sandey, M., Matz, B.M., Thomas, A., Smith, B.F. : | |
| Single-nuclei multiome (ATAC + gene expression) sequencing of a primary canine osteosarcoma elucidates intra-tumoral heterogeneity and characterizes the tumor microenvironment. Int J Mol Sci 24:16365, 2023. Pubmed reference: 38003552. DOI: 10.3390/ijms242216365. | |
| O'Neill, D.G., Edmunds, G.L., Urquhart-Gilmore, J., Church, D.B., Rutherford, L., Smalley, M.J., Brodbelt, D.C. : | |
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| Large Scale Comparative Deconvolution Analysis of the Canine and Human Osteosarcoma Tumor Microenvironment Uncovers Conserved Clinically Relevant Subtypes. bioRxiv , 2023. Pubmed reference: 37808704. DOI: 10.1101/2023.09.27.559797. | |
| Rivera, P.L., Li, W.T., Bhogal, S., Mandell, J.B., Belayneh, R., Hankins, M.L., Payne, J.T., Watters, R.J., Weiss, K.R. : | |
| Antioxidant 1 copper chaperone gene expression and copper levels in dog osteosarcoma patients. Vet Comp Oncol 21:559-564, 2023. Pubmed reference: 37148200. DOI: 10.1111/vco.12903. | |
| Romanucci, M., De Maria, R., Morello, E.M., Della Salda, L. : | |
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| Sarver, A.L., Mills, L.J., Makielski, K.M., Temiz, N.A., Wang, J., Spector, L.G., Subramanian, S., Modiano, J.F. : | |
| Distinct mechanisms of PTEN inactivation in dogs and humans highlight convergent molecular events that drive cell division in the pathogenesis of osteosarcoma. Cancer Genet 276-277:1-11, 2023. Pubmed reference: 37267683. DOI: 10.1016/j.cancergen.2023.05.001. | |
| Silver, K.I., Patkar, S., Mazcko, C., Berger, E.P., Beck, J.A., LeBlanc, A.K. : | |
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| Tan, L., Wang, Y., Hu, X., Du, G., Tang, X., Min, L. : | |
| Advances of osteosarcoma models for drug discovery and precision medicine. Biomolecules 13:1362, 2023. Pubmed reference: 37759763. DOI: 10.3390/biom13091362. | |
| Tarone, L., Giacobino, D., Camerino, M., Maniscalco, L., Iussich, S., Parisi, L., Giovannini, G., Dentini, A., Bolli, E., Quaglino, E., Merighi, I.F., Morello, E., Buracco, P., Riccardo, F., Cavallo, F. : | |
| A chimeric human/dog-DNA vaccine against CSPG4 induces immunity with therapeutic potential in comparative preclinical models of osteosarcoma. Mol Ther 31:2342-2359, 2023. Pubmed reference: 37312451. DOI: 10.1016/j.ymthe.2023.06.004. | |
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| Establishment and characterization of cell lines from canine metastatic osteosarcoma. Cells 13:25, 2023. Pubmed reference: 38201229. DOI: 10.3390/cells13010025. | |
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| 2021 | Das, S., Idate, R., Regan, D.P., Fowles, J.S., Lana, S.E., Thamm, D.H., Gustafson, D.L., Duval, D.L. : |
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| Genome-wide analyses for osteosarcoma in Leonberger dogs reveal the CDKN2A/B gene locus as a major risk locus. Genes (Basel) 12:1964, 2021. Pubmed reference: 34946912. DOI: 10.3390/genes12121964. | |
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| Momen, M., Kohler, N.L., Binversie, E.E., Dentino, M., Sample, S.J. : | |
| Heritability and genetic variance estimation of osteosarcoma (OSA) in Irish Wolfhound, using deep pedigree information. Canine Med Genet 8:9, 2021. Pubmed reference: 34627404. DOI: 10.1186/s40575-021-00109-y. | |
| Wilk, S.S., Zabielska-Koczywąs, K.A. : | |
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| Canine osteosarcoma genome sequencing identifies recurrent mutations in DMD and the histone methyltransferase gene SETD2. Commun Biol 2:266, 2019. Pubmed reference: 31341965. DOI: 10.1038/s42003-019-0487-2. | |
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| 2017 | Al-Khan, A.A., Gunn, H.J., Day, M.J., Tayebi, M., Ryan, S.D., Kuntz, C.A., Saad, E.S., Richardson, S.J., Danks, J.A. : |
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| 2015 | Szewczyk, M., Lechowski, R., Zabielska, K. : |
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| 2014 | Davis, B.W., Ostrander, E.A. : |
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| 2013 | Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. : |
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| Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B. Genome Biol 14:R132, 2013. Pubmed reference: 24330828. DOI: 10.1186/gb-2013-14-12-r132. | |
| 2012 | Tsai, P.C., Breen, M. : |
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| 2010 | Morello, E., Martano, M., Buracco, P. : |
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| A novel locus for canine osteosarcoma (OSA1) maps to CFA34, the canine orthologue of human 3q26. Genomics 96:220-7, 2010. Pubmed reference: 20647041. DOI: 10.1016/j.ygeno.2010.07.002. | |
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| Cloning and expression of canine CD25 for validation of an anti-human CD25 antibody to compare T regulatory lymphocytes in healthy dogs and dogs with osteosarcoma. Vet Immunol Immunopathol 135:137-45, 2010. Pubmed reference: 20197202. DOI: 10.1016/j.vetimm.2010.02.002. | |
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| Association of blood monocyte and lymphocyte count and disease-free interval in dogs with osteosarcoma. J Vet Intern Med 24:1439-44, 2010. Pubmed reference: 20840314. DOI: 10.1111/j.1939-1676.2010.0591.x. | |
| 2009 | Fossey, SL., Liao, AT., McCleese, JK., Bear, MD., Lin, J., Li, PK., Kisseberth, WC., London, CA. : |
| Characterization of STAT3 activation and expression in canine and human osteosarcoma. BMC Cancer 9:81, 2009. Pubmed reference: 7704483. DOI: 10.3109/10611869408996814. | |
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| Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times. Mol Cancer 8:72, 2009. Pubmed reference: 14761893. DOI: 10.1152/ajpcell.00407.2003. | |
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| Influence of genetic background on tumor karyotypes: evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma. Chromosome Res 17:365-77, 2009. Pubmed reference: 19337847. DOI: 10.1007/s10577-009-9028-z. | |
| 2008 | Kirpensteijn, J., Kik, M., Teske, E., Rutteman, GR. : |
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| 2007 | Phillips, JC., Stephenson, B., Hauck, M., Dillberger, J. : |
| Heritability and segregation analysis of osteosarcoma in the Scottish deerhound. Genomics 90:354-63, 2007. Pubmed reference: 17628392. DOI: 10.1016/j.ygeno.2007.05.001. | |
| 2006 | Khanna, C., Lindblad-Toh, K., Vail, D., London, C., Bergman, P., Barber, L., Breen, M., Kitchell, B., McNeil, E., Modiano, JF., Niemi, S., Comstock, KE., Ostrander, E., Westmoreland, S., Withrow, S. : |
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- Created by Frank Nicholas on 02 Nov 2010
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