OMIA:001441-9615 : Osteosarcoma in Canis lupus familiaris

Categories: Neoplasm

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Somatic mutation

Considered a defect: 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 ..."

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, German Shepherd Dog, Great Dane, Greyhound, Irish Setter, Irish Wolfhound, Leonberger, Rottweiler, Saint Bernard, Scottish Deerhound.


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.

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 :, 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.
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 :, 2023. Pubmed reference: 37148200 . DOI: 10.1111/vco.12903.
Romanucci, M., De Maria, R., Morello, E.M., Della Salda, L. :
Editorial: Canine osteosarcoma as a model in comparative oncology: Advances and perspective. Front Vet Sci 10:1141666, 2023. Pubmed reference: 36798142 . DOI: 10.3389/fvets.2023.1141666.
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.
Wade, C.M., Nuttall, R., Liu, S. :
Comprehensive analysis of geographic and breed-purpose influences on genetic diversity and inherited disease risk in the Doberman dog breed. Canine Med Genet 10:7, 2023. Pubmed reference: 37277858 . DOI: 10.1186/s40575-023-00130-3.
Williams, K., Parker, S., MacDonald-Dickinson, V. :
Risk factors for appendicular osteosarcoma occurrence in large and giant breed dogs in western Canada. Can Vet J 64:167-173, 2023. Pubmed reference: 36733647 .
2022 Beck, J., Ren, L., Huang, S., Berger, E., Bardales, K., Mannheimer, J., Mazcko, C., LeBlanc, A. :
Canine and murine models of osteosarcoma. Vet Pathol 59:399-414, 2022. Pubmed reference: 35341404 . DOI: 10.1177/03009858221083038.
2021 Das, S., Idate, R., Regan, D.P., Fowles, J.S., Lana, S.E., Thamm, D.H., Gustafson, D.L., Duval, D.L. :
Immune pathways and TP53 missense mutations are associated with longer survival in canine osteosarcoma. Commun Biol 4:1178, 2021. Pubmed reference: 34635775 . DOI: 10.1038/s42003-021-02683-0.
Jarvis, S., Koumadoraki, E., Madouros, N., Sharif, S., Saleem, A., Khan, S. :
Non-rodent animal models of osteosarcoma: A review. Cancer Treat Res Commun 27:100307, 2021. Pubmed reference: 33453605 . DOI: 10.1016/j.ctarc.2021.100307.
Kerboeuf, M., Koppang, E.O., Haaland, A.H., Lingaas, F., Bruland, Ø.S., Teige, J., Moe, L. :
Early immunohistochemical detection of pulmonary micrometastases in dogs with osteosarcoma. Acta Vet Scand 63:41, 2021. Pubmed reference: 34732227 . DOI: 10.1186/s13028-021-00608-9.
Letko, A., Minor, K.M., Norton, E.M., Marinescu, V.D., Drögemüller, M., Ivansson, E., Megquier, K., Noh, H.J., Starkey, M., Friedenberg, S.G., Lindblad-Toh, K., Mickelson, J.R., Drögemüller, C. :
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.
Luu, A.K., Wood, G.A., Viloria-Petit, A.M. :
Recent advances in the discovery of biomarkers for canine osteosarcoma. Front Vet Sci 8:734965, 2021. Pubmed reference: 34660770 . DOI: 10.3389/fvets.2021.734965.
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. :
Molecular mechanisms of canine osteosarcoma metastasis. Int J Mol Sci 22:, 2021. Pubmed reference: 33807419 . DOI: 10.3390/ijms22073639.
2019 Makielski, K.M., Mills, L.J., Sarver, A.L., Henson, M.S., Spector, L.G., Naik, S., Modiano, J.F. :
Risk factors for development of canine and human osteosarcoma: A comparative review. Vet Sci 6:, 2019. Pubmed reference: 31130627 . DOI: 10.3390/vetsci6020048.
Zapata, I., Moraes, L.E., Fiala, E.M., Zaldivar-Lopez, S., Couto, C.G., Rowell, J.L., Alvarez, C.E. :
Risk-modeling of dog osteosarcoma genome scans shows individuals with Mendelian-level polygenic risk are common. BMC Genomics 20:226, 2019. Pubmed reference: 30890123 . DOI: 10.1186/s12864-019-5531-6.
2018 Sakthikumar, S., Elvers, I., Kim, J., Arendt, M.L., Thomas, R., Turner-Maier, J., Swofford, R., Johnson, J., Schumacher, S.E., Alföldi, J., Axelsson, E., Couto, C.G., Kisseberth, W.C., Pettersson, M.E., Getz, G., Meadows, J.R.S., Modiano, J.F., Breen, M., Kierczak, M., Forsberg-Nilsson, K., Marinescu, V.D., Lindblad-Toh, K. :
SETD2 is recurrently mutated in whole-exome sequenced canine osteosarcoma. Cancer Res 78:3421-3431, 2018. Pubmed reference: 29724721 . DOI: 10.1158/0008-5472.CAN-17-3558.
Shao, Y.W., Wood, G.A., Lu, J., Tang, Q.L., Liu, J., Molyneux, S., Chen, Y., Fang, H., Adissu, H., McKee, T., Waterhouse, P., Khokha, R. :
Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma. Oncogene :, 2018. Pubmed reference: 30093633 . DOI: 10.1038/s41388-018-0444-4.
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. :
Immunohistochemical validation of spontaneously arising canine osteosarcoma as a model for human osteosarcoma. J Comp Pathol 157:256-265, 2017. Pubmed reference: 29169619 . DOI: 10.1016/j.jcpa.2017.07.005.
Sapierzyński, R., Czopowicz, M. :
The animal-dependent risk factors in canine osteosarcomas. Pol J Vet Sci 20:293-298, 2017. Pubmed reference: 28865206 . DOI: 10.1515/pjvs-2017-0035.
2015 Szewczyk, M., Lechowski, R., Zabielska, K. :
What do we know about canine osteosarcoma treatment? Review. Vet Res Commun 39:61-7, 2015. Pubmed reference: 25422073 . DOI: 10.1007/s11259-014-9623-0.
2014 Davis, B.W., Ostrander, E.A. :
Domestic dogs and cancer research: a breed-based genomics approach. ILAR J 55:59-68, 2014. Pubmed reference: 24936030 . DOI: 10.1093/ilar/ilu017.
Fenger, J.M., London, C.A., Kisseberth, W.C. :
Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J 55:69-85, 2014. Pubmed reference: 24936031 . DOI: 10.1093/ilar/ilu009.
2013 Bellumori, T.P., Famula, T.R., Bannasch, D.L., Belanger, J.M., Oberbauer, A.M. :
Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc 242:1549-55, 2013. Pubmed reference: 23683021 . DOI: 10.2460/javma.242.11.1549.
Dobson, J.M. :
Breed-predispositions to cancer in pedigree dogs. ISRN Vet Sci 2013:941275, 2013. Pubmed reference: 23738139 . DOI: 10.1155/2013/941275.
Karlsson, E.K., Sigurdsson, S., Ivansson, E., Thomas, R., Elvers, I., Wright, J., Howald, C., Tonomura, N., Perloski, M., Swofford, R., Biagi, T., Fryc, S., Anderson, N., Courtay-Cahen, C., Youell, L., Ricketts, S.L., Mandlebaum, S., Rivera, P., von Euler, H., Kisseberth, W.C., London, C.A., Lander, E.S., Couto, G., Comstock, K., Starkey, M.P., Modiano, J.F., Breen, M., Lindblad-Toh, K. :
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. :
Array-based comparative genomic hybridization-guided identification of reference genes for normalization of real-time quantitative polymerase chain reaction assay data for lymphomas, histiocytic sarcomas, and osteosarcomas of dogs. Am J Vet Res 73:1335-43, 2012. Pubmed reference: 22924713 . DOI: 10.2460/ajvr.73.9.1335.
2010 Morello, E., Martano, M., Buracco, P. :
Biology, diagnosis and treatment of canine appendicular osteosarcoma: Similarities and differences with human osteosarcoma. Vet J :, 2010. Pubmed reference: 20889358 . DOI: 10.1016/j.tvjl.2010.08.014.
O'Donoghue, LE., Ptitsyn, AA., Kamstock, DA., Siebert, J., Thomas, RS., Duval, DL. :
Expression profiling in canine osteosarcoma: identification of biomarkers and pathways associated with outcome. BMC Cancer 10:506, 2010. Pubmed reference: 20860831 . DOI: 10.1186/1471-2407-10-506.
Phillips, JC., Lembcke, L., Chamberlin, T. :
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.
Rissetto, KC., Rindt, H., Selting, KA., Villamil, JA., Henry, CJ., Reinero, CR. :
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.
Selvarajah, GT., Kirpensteijn, J. :
Prognostic and predictive biomarkers of canine osteosarcoma. Vet J 185:28-35, 2010. Pubmed reference: 20493743 . DOI: 10.1016/j.tvjl.2010.04.010.
Sottnik, JL., Rao, S., Lafferty, MH., Thamm, DH., Morley, PS., Withrow, SJ., Dow, SW. :
Association of blood monocyte and lymphocyte count and disease-free interval in dogs with osteosarcoma. J Vet Intern Med :, 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.
Selvarajah, GT., Kirpensteijn, J., van Wolferen, ME., Rao, NA., Fieten, H., Mol, JA. :
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.
Thomas, R., Wang, HJ., Tsai, PC., Langford, CF., Fosmire, SP., Jubala, CM., Getzy, DM., Cutter, GR., Modiano, JF., Breen, M. :
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. :
TP53 gene mutations in canine osteosarcoma. Vet Surg 37:454-60, 2008. Pubmed reference: 18986312 . DOI: 10.1111/j.1532-950X.2008.00407.x.
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. :
The dog as a cancer model. Nat Biotechnol 24:1065-6, 2006. Pubmed reference: 16964204 . DOI: 10.1038/nbt0906-1065b.
2005 Dow, S., Elmslie, R., Kurzman, I., MacEwen, G., Pericle, F., Liggitt, D. :
Phase I study of liposome-DNA complexes encoding the interleukin-2 gene in dogs with osteosarcoma lung metastases. Hum Gene Ther 16:937-46, 2005. Pubmed reference: 16076252 . DOI: 10.1089/hum.2005.16.937.
Mullins, MN., Lana, SE., Dernell, WS., Ogilvie, GK., Withrow, SJ., Ehrhart, EJ. :
Cyclooxygenase-2 expression in canine appendicular osteosarcomas. J Vet Intern Med 18:859-65, 2005. Pubmed reference: 15638270 .
2004 Flint, AF., U'Ren, L., Legare, ME., Withrow, SJ., Dernell, W., Hanneman, WH. :
Overexpression of the erbB-2 proto-oncogene in canine osteosarcoma cell lines and tumors. Vet Pathol 41:291-6, 2004. Pubmed reference: 15133183 . DOI: 10.1354/vp.41-3-291.
Khanna, C., Wan, X., Bose, S., Cassaday, R., Olomu, O., Mendoza, A., Yeung, C., Gorlick, R., Hewitt, SM., Helman, LJ. :
The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med 10:182-6, 2004. Pubmed reference: 14704791 . DOI: 10.1038/nm982.
2003 MacEwen, EG., Kutzke, J., Carew, J., Pastor, J., Schmidt, JA., Tsan, R., Thamm, DH., Radinsky, R. :
c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells. Clin Exp Metastasis 20:421-30, 2003. Pubmed reference: 14524531 .
2002 Levine, RA., Forest, T., Smith, C. :
Tumor suppressor PTEN is mutated in canine osteosarcoma cell lines and tumors. Vet Pathol 39:372-8, 2002. Pubmed reference: 12014501 .
Levine, RA. :
Overexpression of the sis oncogene in a canine osteosarcoma cell line. Vet Pathol 39:411-2, 2002. Pubmed reference: 12014510 .
2000 Ferracini, R., Angelini, P., Cagliero, E., Linari, A., Martano, M., Wunder, J., Buracco, P. :
MET oncogene aberrant expression in canine osteosarcoma. J Orthop Res 18:253-6, 2000. Pubmed reference: 10815826 . DOI: 10.1002/jor.1100180213.
1999 Mendoza, S., Konishi, T., Dernell, WS., Withrow, SJ., Miller, CW. :
Status of the p53, Rb and MDM2 genes in canine osteosarcoma. Anticancer Res 18:4449-53, 1999. Pubmed reference: 9891508 .
1998 Johnson, AS., Couto, CG., Weghorst, CM. :
Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog. Carcinogenesis 19:213-7, 1998. Pubmed reference: 9472714 .
Ru, G., Terracini, B., Glickman, LT. :
Host related risk factors for canine osteosarcoma. Vet J 156:31-9, 1998. Pubmed reference: 9691849 .
1997 van Leeuwen, IS., Cornelisse, CJ., Misdorp, W., Goedegebuure, SA., Kirpensteijn, J., Rutteman, GR. :
P53 gene mutations in osteosarcomas in the dog. Cancer Lett 111:173-8, 1997. Pubmed reference: 9022143 .
1996 Sagartz, JE., Bodley, WL., Gamblin, RM., Couto, CG., Tierney, LA., Capen, CC. :
p53 tumor suppressor protein overexpression in osteogenic tumors of dogs. Vet Pathol 33:213-21, 1996. Pubmed reference: 8801715 .

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  • Created by Frank Nicholas on 02 Nov 2010
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