OMIA 000620-9615 : Histiocytosis, malignant in Canis lupus familiaris

In other species: domestic cat , pig , cattle

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Year key variant first reported: 2017

Cross-species summary: This is a familial form of cancer. Also known as histiocytic sarcoma (HS)

History: The GWAS reported by Shearin et al. (2012) was "the first GWAS for histiocytic sarcoma in any species".

Inheritance: After examining the family data pertaining to 127 cases in Bermese mountain dogs, Padgett et al. (1995) concluded that the data were not consistent with any of the simple, single-locus models of inheritance. Considering it as a multifactorial disorder, they estimated the heritability of liability to be 0.30.

Mapping: The GWAS conducted with the Canine SNP20 Beadchip by Shearin et al. (2012) on affected and non-affected Bernese Mountain dogs from Europe and the USA identified a single region on chromosome CFA11. Fine-mapping and sequencing implicated "a single haplotype spanning MTAP and part of CDKN2A".

Asada et al. (2017) reported that "a 2-base (AT) insertion in exon 5 [of TP53], resulting in the introduction of a stop codon (c.446_447insAT, p.Tyr150SerfsX8)" is associated with histiocytic sarcoma in numerous breeds.

Genetic testing: A "pre-test", based on the results of Shearin et al. (2012) is available from Antagene: http://www.antagene.com/en/commander/histiocytic-sarcoma-pre-test.

Given the results reported by Asada et al. (2019), namely that "The mutation was detected in [only] 26 of 64 [affected] dogs (41%)" and their conclusion "that HS cells might acquire insAT in the TP53 gene during development of metastasis, but insAT was not a prognostic factor in canine HS", it would seem that insAT is not a useful marker. It has, therefore, been removed from the OMIA table of likely causal variants.

Breeds: Bernese Mountain dog, Flat-coated retriever, Golden Retriever, Rottweiler.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
TP53 tumor protein p53 Canis lupus familiaris 5 NC_006587.3 (32565149..32561406) TP53 Homologene, Ensembl, NCBI gene

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 Asada, H., Tomiyasu, H., Okada, K., Chambers, J.K., Goto-Koshino, Y., Uchida, K., Kagawa, Y., Ohno, K., Tsujimoto, H. :
Clinical significance of the two-base insertion mutation in the TP53 gene in canine histiocytic sarcoma. Res Vet Sci 124:57-60, 2019. Pubmed reference: 30852355. DOI: 10.1016/j.rvsc.2019.03.003.
Kennedy, K., Thomas, R., Durrant, J., Jiang, T., Motsinger-Reif, A., Breen, M. :
Genome-wide DNA copy number analysis and targeted transcriptional analysis of canine histiocytic malignancies identifies diagnostic signatures and highlights disruption of spindle assembly complex. Chromosome Res :, 2019. Pubmed reference: 31011867. DOI: 10.1007/s10577-019-09606-0.
2017 Asada, H., Tsuboi, M., Chambers, J.K., Uchida, K., Tomiyasu, H., Goto-Koshino, Y., Ohno, K., Tsujimoto, H. :
A 2-base insertion in exon 5 is a common mutation of the TP53 gene in dogs with histiocytic sarcoma. J Vet Med Sci :, 2017. Pubmed reference: 28867679. DOI: 10.1292/jvms.17-0197.
2015 Heinrich, F., Contioso, V.B., Stein, V.M., Carlson, R., Tipold, A., Ulrich, R., Puff, C., Baumgärtner, W., Spitzbarth, I. :
Passage-dependent morphological and phenotypical changes of a canine histiocytic sarcoma cell line (DH82 cells). Vet Immunol Immunopathol 163:86-92, 2015. Pubmed reference: 25534080. DOI: 10.1016/j.vetimm.2014.11.006.
Mariani, C.L., Jennings, M.K., Olby, N.J., Borst, L.B., Brown, J.C., Robertson, I.D., Seiler, G.S., MacKillop, E. :
Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006-2012). J Vet Intern Med 29:607-13, 2015. Pubmed reference: 25711602. DOI: 10.1111/jvim.12554.
2014 Barrett, L.E., Pollard, R.E., Zwingenberger, A., Zierenberg-Ripoll, A., Skorupski, K.A. :
Radiographic characterization of primary lung tumors in 74 dogs. Vet Radiol Ultrasound 55:480-7, 2014. Pubmed reference: 24674604. DOI: 10.1111/vru.12154.
Boerkamp, K.M., van Steenbeek, F.G., Penning, L.C., Groot Koerkamp, M.J., van Leenen, D., Vos-Loohuis, M., Grinwis, G.C., Rutteman, G.R. :
The two main forms of histiocytic sarcoma in the predisposed Flatcoated retriever dog display variation in gene expression. PLoS One 9:e98258, 2014. Pubmed reference: 24886914. DOI: 10.1371/journal.pone.0098258.
Chikazawa, S., Kitahara, Y., Ando, E., Hori, Y., Hoshi, F., Kanai, K., Ito, N., Higuchi, S. :
Erythrophagocytosis enhances heme-dependent cytotoxicity of antimalarial drugs in canine histiocytic sarcoma cell line DH82. J Vet Med Sci 76:249-53, 2014. Pubmed reference: 24065080.
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.
Denstedt, E. :
Suspected disseminated histiocytic sarcoma in a 3-year-old Perro de Presa Canario dog. Can Vet J 55:181-4, 2014. Pubmed reference: 24489399.
Empl, M.T., Macke, S., Winterhalter, P., Puff, C., Lapp, S., Stoica, G., Baumgärtner, W., Steinberg, P. :
The growth of the canine glioblastoma cell line D-GBM and the canine histiocytic sarcoma cell line DH82 is inhibited by the resveratrol oligomers hopeaphenol and r2-viniferin. Vet Comp Oncol 12:149-59, 2014. Pubmed reference: 22882564. DOI: 10.1111/j.1476-5829.2012.00349.x.
Moore, P.F. :
A review of histiocytic diseases of dogs and cats. Vet Pathol 51:167-84, 2014. Pubmed reference: 24395976. DOI: 10.1177/0300985813510413.
Takahashi, M., Tomiyasu, H., Hotta, E., Asada, H., Fukushima, K., Kanemoto, H., Fujino, Y., Ohno, K., Uchida, K., Nakayama, H., Tsujimoto, H. :
Clinical characteristics and prognostic factors in dogs with histiocytic sarcomas in Japan. J Vet Med Sci 76:661-6, 2014. Pubmed reference: 24441652.
VanderHart, D.J., Reese, D.J., Greenberg, S.M. :
What is your diagnosis? Histiocytic sarcoma. J Am Vet Med Assoc 244:899-901, 2014. Pubmed reference: 24697763. DOI: 10.2460/javma.244.8.899.
2013 Boerkamp, K.M., van der Kooij, M., van Steenbeek, F.G., van Wolferen, M.E., Groot Koerkamp, M.J., van Leenen, D., Grinwis, G.C., Penning, L.C., Wiemer, E.A., Rutteman, G.R. :
Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog. PLoS One 8:e71094, 2013. Pubmed reference: 23936488. DOI: 10.1371/journal.pone.0071094.
Dobson, J.M. :
Breed-predispositions to cancer in pedigree dogs. ISRN Vet Sci 2013:941275, 2013. Pubmed reference: 23738139. DOI: 10.1155/2013/941275.
Erich, S.A., Rutteman, G.R., Teske, E. :
Causes of death and the impact of histiocytic sarcoma on the life expectancy of the Dutch population of Bernese mountain dogs and Flat-coated retrievers. Vet J 198:678-83, 2013. Pubmed reference: 24231621. DOI: 10.1016/j.tvjl.2013.09.062.
Ito, K., Kuroki, S., Kobayashi, M., Ono, K., Washizu, T., Bonkobara, M. :
Identification of dasatinib as an in vitro potent growth inhibitor of canine histiocytic sarcoma cells. Vet J 196:536-40, 2013. Pubmed reference: 23369384. DOI: 10.1016/j.tvjl.2012.12.016.
Nikolic Nielsen, L., Kjelgaard-Hansen, M., Kristensen, A.T. :
Monocyte chemotactic protein-1 and other inflammatory parameters in Bernese Mountain dogs with disseminated histiocytic sarcoma. Vet J 198:424-8, 2013. Pubmed reference: 23992872. DOI: 10.1016/j.tvjl.2013.07.030.
Silva, G., Fachin, A.L., Beleboni, R.O., França, S.C., Marins, M. :
In vitro action of flavonoids in the canine malignant histiocytic cell line DH82. Molecules 18:15448-63, 2013. Pubmed reference: 24352006. DOI: 10.3390/molecules181215448.
Thakkar, P., Pease, A.P., Guiot, L.P., Fitzgerald, S.D., Adu Addai, B., Smedley, R.C. :
What is your diagnosis? Disseminated histiocytic sarcoma. J Am Vet Med Assoc 243:1255-7, 2013. Pubmed reference: 24134574. DOI: 10.2460/javma.243.9.1255.
Yamazaki, H., Takagi, S., Hoshino, Y., Hosoya, K., Okumura, M. :
Inhibition of survivin influences the biological activities of canine histiocytic sarcoma cell lines. PLoS One 8:e79810, 2013. Pubmed reference: 24260303. DOI: 10.1371/journal.pone.0079810.
Yamazaki, H., Takagi, S., Oh, N., Hoshino, Y., Hosoya, K., Okumura, M. :
Comparative analysis of mRNA expression of surface antigens between histiocytic and nonhistiocytic sarcoma in dogs. J Vet Intern Med 28:204-10, 2013. Pubmed reference: 24428323. DOI: 10.1111/jvim.12244.
van Kuijk, L., van Ginkel, K., de Vos, J.P., Brearley, M.J., Butinar, J., Gielen, I., van Garderen, E., Chiers, K., Verhoeven, P.S. :
Peri-articular histiocytic sarcoma and previous joint disease in Bernese Mountain Dogs. J Vet Intern Med 27:293-9, 2013. Pubmed reference: 23458888. DOI: 10.1111/jvim.12059.
2012 Arnold, E.J., Pressler, B.M., Heng, H.G. :
What is your diagnosis? Histiocytic sarcoma. J Am Vet Med Assoc 240:821-3, 2012. Pubmed reference: 22443434. DOI: 10.2460/javma.240.7.821.
Hafeman, S.D., Varland, D., Dow, S.W. :
Bisphosphonates significantly increase the activity of doxorubicin or vincristine against canine malignant histiocytosis cells. Vet Comp Oncol 10:44-56, 2012. Pubmed reference: 22236140. DOI: 10.1111/j.1476-5829.2011.00274.x.
Mastrorilli, C., Spangler, E.A., Christopherson, P.W., Aubry, O.A., Newton, J.C., Smith, A.N., Kennis, R.A., Weismann, J.L., Moore, P.F. :
Multifocal cutaneous histiocytic sarcoma in a young dog and review of histiocytic cell immunophenotyping. Vet Clin Pathol 41:412-8, 2012. Pubmed reference: 22747712. DOI: 10.1111/j.1939-165X.2012.00449.x.
Nielsen, L.N., McEvoy, F., Jessen, L.R., Kristensen, A.T. :
Investigation of a screening programme and the possible identification of biomarkers for early disseminated histiocytic sarcoma in Bernese Mountain dogs. Vet Comp Oncol 10:124-34, 2012. Pubmed reference: 22235831. DOI: 10.1111/j.1476-5829.2011.00285.x.
Sapierzyński, R., Jagielski, D., Dolka, I., Fabisiak, M. :
Cytopathological diagnosis of visceral histiocytic sarcoma in five dogs. Pol J Vet Sci 15:751-8, 2012. Pubmed reference: 23390766.
Shearin, A.L., Hedan, B., Cadieu, E., Erich, S.A., Schmidt, E.V., Faden, D.L., Cullen, J., Abadie, J., Kwon, E.M., Gröne, A., Devauchelle, P., Rimbault, M., Karyadi, D.M., Lynch, M., Galibert, F., Breen, M., Rutteman, G.R., André, C., Parker, H.G., Ostrander, E.A. :
The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine cancer. Cancer Epidemiol Biomarkers Prev 21:1019-27, 2012. Pubmed reference: 22623710. DOI: 10.1158/1055-9965.EPI-12-0190-T.
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.
Tsai, S., Sutherland-Smith, J., Burgess, K., Ruthazer, R., Sato, A. :
Imaging characteristics of intrathoracic histiocytic sarcoma in dogs. Vet Radiol Ultrasound 53:21-7, 2012. Pubmed reference: 21831241. DOI: 10.1111/j.1740-8261.2011.01863.x.
2011 Constantino-Casas, F., Mayhew, D., Hoather, T.M., Dobson, J.M. :
The clinical presentation and histopathologic-immunohistochemical classification of histiocytic sarcomas in the Flat Coated Retriever. Vet Pathol 48:764-71, 2011. Pubmed reference: 20930108. DOI: 10.1177/0300985810385153.
Hedan, B., Thomas, R., Motsinger-Reif, A., Abadie, J., Andre, C., Cullen, J., Breen, M. :
Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior. BMC Cancer 11:201, 2011. Pubmed reference: 21615919. DOI: 10.1186/1471-2407-11-201.
Klahn, S.L., Kitchell, B.E., Dervisis, N.G. :
Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcoma. J Am Vet Med Assoc 239:90-6, 2011. Pubmed reference: 21718201. DOI: 10.2460/javma.239.1.90.
Soare, T., Noble, P.J., Hetzel, U., Fonfara, S., Kipar, A. :
Paraneoplastic syndrome in haemophagocytic histiocytic sarcoma in a dog. J Comp Pathol 146:168-74, 2011. Pubmed reference: 21741052. DOI: 10.1016/j.jcpa.2011.05.006.
Sterenczak, K.A., Kleinschmidt, S., Wefstaedt, P., Eberle, N., Hewicker-Trautwein, M., Bullerdiek, J., Nolte, I., Murua Escobar, H. :
Quantitative PCR and immunohistochemical analyses of HMGB1 and RAGE expression in canine disseminated histiocytic sarcoma (malignant histiocytosis). Anticancer Res 31:1541-8, 2011. Pubmed reference: 21617208.
2010 André, C., Abadie, J., Hedan, B., de Brito, C., Lagadic, M., Poujade, A., Devauchelle, P. :
Proliférations histiocytaires canines. D’après une étude épidémiologique, clinique et génétique de 100 cas de sarcome histiocytaire chez le Bouvier bernois. [Canine histiocytic proliferations. From an epidemiological, clinical, and genetic study of 100 histiocytic sarcomas in the Bernese mountain dog breed] Pratique médicale et chirurgicale de l’animal de compagnie (PMAC) 45:9-17, 2010.
Castellanos, V.C., O'Neill, S., Seiler, G.S. :
What is your diagnosis? Histiocytic sarcoma. J Am Vet Med Assoc 236:1293-4, 2010. Pubmed reference: 20550442. DOI: 10.2460/javma.236.12.1293.
Friedrichs, K.R., Thomas, C., Plier, M., Andrews, G.A., Chavey, P.S., Young, K.M. :
Evaluation of serum ferritin as a tumor marker for canine histiocytic sarcoma. J Vet Intern Med 24:904-11, 2010. Pubmed reference: 20561186. DOI: 10.1111/j.1939-1676.2010.0543.x.
Hafeman, S., London, C., Elmslie, R., Dow, S. :
Evaluation of liposomal clodronate for treatment of malignant histiocytosis in dogs. Cancer Immunol Immunother 59:441-52, 2010. Pubmed reference: 19760220. DOI: 10.1007/s00262-009-0763-y.
Nielsen, L., Andreasen, SN., Andersen, SD., Kristensen, AT. :
Malignant histiocytosis and other causes of death in Bernese mountain dogs in Denmark. Vet Rec 166:199-202, 2010. Pubmed reference: 20154310. DOI: 10.1136/vr.b4756.
Rassnick, K.M., Moore, A.S., Russell, D.S., Northrup, N.C., Kristal, O., Bailey, D.B., Flory, A.B., Kiselow, M.A., Intile, J.L. :
Phase II, open-label trial of single-agent CCNU in dogs with previously untreated histiocytic sarcoma. J Vet Intern Med 24:1528-31, 2010. Pubmed reference: 21155191.
2009 Abadie, J., Hédan, B., Cadieu, E., De Brito, C., Devauchelle, P., Bourgain, C., Parker, H.G., Vaysse, A., Margaritte-Jeannin, P., Galibert, F., Ostrander, E.A., André, C. :
Epidemiology, pathology, and genetics of histiocytic sarcoma in the Bernese mountain dog breed. J Hered 100 Suppl 1:S19-27, 2009. Pubmed reference: 19531730. DOI: 10.1093/jhered/esp039.
Maruo, T., Namikawa, K., Kunihiro, A., Lynch, J., Shida, T., Kishikawa, S. :
Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog. J S Afr Vet Assoc 80:261-3, 2009. Pubmed reference: 20458870.
Wagter, H.W., Vos, A.J., van den Ingh, T. :
[A localised histocytic sarcoma in the stomach of a dog]. Tijdschr Diergeneeskd 134:526-8, 2009. Pubmed reference: 19579381.
2008 Coleman, K.D., Lurie, D.M., Blaik, M.A., Demuth, G., Kirkby, K. :
What is your diagnosis? Histiocytic sarcoma. J Am Vet Med Assoc 232:1801-2, 2008. Pubmed reference: 18598147. DOI: 10.2460/javma.232.12.1801.
2007 Fulmer, A.K., Mauldin, G.E. :
Canine histiocytic neoplasia: an overview. Can Vet J 48:1041-3, 1046-50, 2007. Pubmed reference: 17987966.
Schultz, R.M., Puchalski, S.M., Kent, M., Moore, P.F. :
Skeletal lesions of histiocytic sarcoma in nineteen dogs. Vet Radiol Ultrasound 48:539-43, 2007. Pubmed reference: 18018725.
2006 Dobson, J., Villiers, E., Roulois, A., Gould, S., Mellor, P., Hoather, T., Watson, P. :
Histiocytic sarcoma of the spleen in flat-coated retrievers with regenerative anaemia and hypoproteinaemia. Vet Rec 158:825-9, 2006. Pubmed reference: 16782856.
Soller, J.T., Murua Escobar, H., Janssen, M., Fork, M., Bullerdiek, J., Nolte, I. :
Cytokine genes single nucleotide polymorphism (SNP) screening analyses in canine malignant histiocytosis. Anticancer Res 26:3417-20, 2006. Pubmed reference: 17094461.
Thio, T., Hilbe, M., Grest, P., Pospischil, A. :
Malignant histiocytosis of the brain in three dogs. J Comp Pathol 134:241-4, 2006. Pubmed reference: 16537081. DOI: 10.1016/j.jcpa.2005.09.005.
Voegeli, E., Welle, M., Hauser, B., Dolf, G., Flückiger, M. :
[Histiocytic sarcoma in the Swiss population of Bernese mountain dogs: a retrospective study of its genetic predisposition]. Schweiz Arch Tierheilkd 148:281-8, 2006. Pubmed reference: 16826705. DOI: 10.1024/0036-7281.148.6.281.
Zavodovskaya, R., Liao, AT., Jones, CL., Yip, B., Chien, MB., Moore, PF., London, CA. :
Evaluation of dysregulation of the receptor tyrosine kinases Kit, Flt3, and Met in histiocytic sarcomas of dogs. Am J Vet Res 67:633-41, 2006. Pubmed reference: 16579756. DOI: 10.2460/ajvr.67.4.633.
1996 Ramsey, I.K., Mckay, J.S., Rudorf, H., Dobson, J.M. :
Malignant histiocytosis in three Bernese Mountain dogs Veterinary Record 138:440-444, 1996. Pubmed reference: 8735262.
1995 Padgett, G.A., Madewell, B.R., Keller, E.T., Todar, L., Packard, M. :
Inheritance of histiocytosis in Bernese mountain dogs Journal of Small Animal Practice 36:93-98, 1995. Pubmed reference: 7783441.
Paterson, S., Boydell, P., Pike, R. :
Systemic histiocytosis in the Bernese mountain dog Journal of Small Animal Practice 36:233-236, 1995. Pubmed reference: 7650919.
1993 Hayden, D.W., Waters, D.J., Burke, B.A., Manivel, J.C. :
Disseminated Malignant Histiocytosis in a Golden Retriever - Clinicopathologic, Ultrastructural, and Immunohistochemical Findings Veterinary Pathology 30:256-264, 1993. Pubmed reference: 8333107.

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  • Created by Frank Nicholas on 13 Jul 2011
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