Canine transmissible venereal tumor
Canine transmissible venereal tumors (CTVTs), also called transmissible venereal tumors (TVTs), canine transmissible venereal sarcoma (CTVS), sticker tumors and infectious sarcoma is a histiocytic tumor of the dog and other canids that mainly affects the external genitalia, and is transmitted from animal to animal during copulation. It is one of only four known transmissible cancers; another is devil facial tumor disease, a cancer which occurs in Tasmanian devils.
The tumor cells are themselves the infectious agents, and the tumors that form are not genetically related to the host dog. Although the genome of a CTVT is derived from a canid (probably a dog, wolf or coyote), it is now essentially living as a unicellular, asexually reproducing (but sexually transmitted) pathogen. Sequence analysis of the genome suggests it diverged from canids over 6,000 years ago; possibly much earlier. The most recent estimates of its time of origin place date it to about 11,000 years ago. However, the most recent common ancestor of extant tumors is more recent: it probably originated 200 to 2,500 years ago.
Canine TVTs were initially described by Russian veterinarian M.A. Novinsky (1841–1914) in 1876, when he demonstrated that the tumor could be transplanted from one dog to another by infecting them with tumor cells.
Canine transmissible venereal tumors are histiocytic tumors that may be transmitted among dogs through coitus, licking, biting and sniffing tumor affected areas. The concept that the tumor is naturally transmissible as an allograft came from three important observations. First, CTVTs can only be experimentally induced by transplanting living tumor cells, and not by killed cells or cell filtrates. Second, the tumor karyotes is aneuploid but has characteristic marker chromosomes in all tumors collected in different geographic regions. Third, a long interspersed nuclear element (LINE-1) insertion near c-myc has been found in all tumors examined so far and can be used as a diagnostic marker to confirm that a tumor is a CTVT.
The CTVT cells have fewer chromosomes than normal cells. Dog cells normally have 78 chromosomes; CTVT cells contain 57–64 chromosomes that are very different in appearance from normal dog chromosomes. All dog chromosomes except X and Y are acrocentric, having a centromere very near to the end of the chromosome, while many of the CTVT chromosomes are metacentric or submetacentric, having a centromere nearer to the middle. There is no evidence that the tumor is caused by a virus or virus-like organism. The infectious agent of canine transmissible venereal tumor is the cancer cell itself and the tumor is clonal in origin. All tumor cells of this type of cancer share extremely similar genetic code, often if not always unrelated to the DNA of their host. Specifically, the LINE-1 element in the tumor cells is in a different location than in normal canine DNA. This demonstrates that the tumors do not arise from separate cancerous transformation in individual animals. Rather, the malignant tumor cells from one dog are transferred to another.
Canine transmissible venereal tumors are most commonly seen in sexually active dogs in tropical and subtropical climates. The disease is spread when dogs mate, and it can even be transmitted to other canine species, such as foxes and coyotes. Spontaneous regression of the tumor can occur, probably due to a response from the immune system. CTVT undergoes a predictable cycle: the initial growth phase of four to six months (P phase), a stable phase, and a regression phase (R phase), although not all CTVTs will regress. The tumor does not often metastasize (occurring in about 5 percent of cases), except in puppies and immunocompromised dogs. Metastasis is most commonly to regional lymph nodes, but can also be seen in the skin, brain, eye, liver, spleen, testicle, and muscle. A biopsy is necessary for diagnosis.
The success of this single cell lineage, believed to be the longest continually propagated cell lineage in the world, can be attributed to the tumor’s mode of transmission in a specific host system. Although direct contact is generally not a highly efficient mode of transfer, CTVTs take advantage of the popular sire effect of domestic dogs. A single male can produce dozens of litters over his lifetime, allowing the tumor to affect many more females than it could if a monogamous species were the host. Understanding the epidemiology of CTVTs is hoped to provide insights for populations that may experience CTVT exposure and information about disease prevalence. Canine transmissible venereal tumors are more often found in temperate climates where there are large populations of stray dogs, but little is known about the details of transmission.
Signs and symptoms
In male dogs, the tumor affects the penis or prepuce. In females, it affects the vagina or labia. Rarely, the mouth or nose are affected. The tumor often has a cauliflower-like appearance. Signs of genital TVT include a discharge from the prepuce and in some cases urinary retention, from blockage of the urethra. Signs of a nasal TVT include orinasal fistulae, nosebleeds and other nasal discharge, facial swelling, and enlargement of the submandibular lymph nodes.
Surgery may be difficult due to the location of these tumors. Surgery alone often leads to recurrence. Chemotherapy is very effective for TVTs. The prognosis for complete remission with chemotherapy is excellent. The most common chemotherapy agents used for TVTs are vincristine, vinblastine, and doxorubicin. Radiation therapy may be effective when chemotherapy does not work.
- Choi, Charles Q. (2006-08-10). "Contagious Canine Cancer Spread by Parasites". LiveScience. Retrieved 2006-08-11.
- Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A (2009). "Origins and Evolution of a Transmissible Cancer". Evolution 63 (9): 2340–2349. doi:10.1111/j.1558-5646.2009.00724.x. PMID 19453727.
- Strakova A, Murchison EP (2015)The cancer which survived: insights from the genome of an 11000 year-old cancer. Curr Opin Genet Dev. 2015 Apr 7;30:49-55. doi: 10.1016/j.gde.2015.03.005
- Murgia, C; Pritchard JK, Kim SY, Fassati A, Weiss RA (2006-08-11). "Clonal Origin and Evolution of a Transmissible Cancer". Cell 126 (3): 477–87. doi:10.1016/j.cell.2006.05.051. PMC 2593932. PMID 16901782.
- Mello Martins, M.I.; de Souza, F. Ferreira; Gobello, C. (2005). "Canine transmissible venereal tumor: Etiology, pathology, diagnosis and treatment". Recent Advances in Small Animal Reproduction. Retrieved 2006-05-25.
- Hasler A, Weber W (2000). "Theriogenology question of the month. Transmissible venereal tumor (TVT)". J. Am. Vet. Med. Assoc. 216 (10): 1557–9. PMID 10825939.
- Dingli D, Nowak MA. Cancer biology: infectious tumour cells. Nature. 2006 Sep 7;443(7107):35–6. B).
- Mukaratirwa S, Gruys E (2003). "Canine transmissible venereal tumour: cytogenetic origin, immunophenotype, and immunobiology. A review". The Veterinary quarterly 25 (3): 101–11. doi:10.1080/01652176.2003.9695151. PMID 14535580.
- Stettner N, Brenner O, Eilam R, Harmelin A (2005). "Pegylated liposomal doxorubicin as a chemotherapeutic agent for treatment of canine transmissible venereal tumor in murine models". J. Vet. Med. Sci. 67 (11): 1133–9. doi:10.1292/jvms.67.1133. PMID 16327225.
- Liao K, Hung S, Hsiao Y, Bennett M, Chu R (2003). "Canine transmissible venereal tumor cell depletion of B lymphocytes: molecule(s) specifically toxic for B cells". Vet. Immunol. Immunopathol. 92 (3–4): 149–62. doi:10.1016/S0165-2427(03)00032-1. PMID 12730015.
- "Canine Transmissible Venereal Tumor: Introduction". The Merck Veterinary Manual. 2006. Retrieved 2007-04-24.
- Rogers K, Walker M, Dillon H (1998). "Transmissible venereal tumor: a retrospective study of 29 cases". Journal of the American Animal Hospital Association 34 (6): 463–70. PMID 9826280.
- Bridgett M. vonHoldt and Elaine A. Ostrander. The Singular History of a Canine Transmissible Tumor. Cell. 126. 2006.
- Morrison, Wallace B. (1998). Cancer in Dogs and Cats (1st ed.). Williams and Wilkins. ISBN 0-683-06105-4.
- Papazoglou L, Koutinas A, Plevraki A, Tontis D (2001). "Primary intranasal transmissible venereal tumour in the dog: a retrospective study of six spontaneous cases". Journal of veterinary medicine. A, Physiology, pathology, clinical medicine 48 (7): 391–400. doi:10.1046/j.1439-0442.2001.00361.x. PMID 11599677.
- Ettinger, Stephen J.;Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 0-7216-6795-3.
- Transmissible Venereal Tumor from The Pet Health Library
- Israel Veterinary Medical Association—Transmissible Venereal Tumors
- New Scientist—Riddle of infectious dog cancer solved
- ScienceDaily—Contagious Cancer In Dogs Confirmed; Origins Traced To Wolves Centuries Ago August 11, 2006 University College London
- LiveScience—Contagious Canine Cancer Spread by Parasites 10 August 2006 10:34 am ET (Charles Q. Choi)
- News @ Nature.com—Dog cancer traced back to wolf roots—200-year-old tumour has mellowed with age Published online: 10 August 2006; | doi:10.1038/news060807-13 (Narelle Towie)
- Veterinary Pathology—Immunohistochemical characterization of canine transmissible venereal tumor Mozos E, Mendez A, Gomez-Villamandos JC, Martin De Las Mulas J, Perez J.Vet Pathol. 1996 May;33(3):257–63.