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Canine transmissible venereal tumor

December 07, 2023

A canine transmissible venereal tumor (CTVT), also known as a transmissible venereal tumor (TVT), canine transmissible venereal sarcoma (CTVS), sticker tumor and infectious sarcoma, is a histiocytic tumor of the external genitalia of the dog and other canines, and is transmitted from animal to animal during mating. It is one of only three known transmissible cancers in mammals; the others are devil facial tumor disease, a cancer which occurs in Tasmanian devils, and contagious reticulum cell sarcoma of the Syrian hamster.

Illustration of venereal granulomata on a dog's penis

The tumor cells are themselves the infectious agents, and the tumors that form are not genetically related to the host dog.[1] Although the genome of a CTVT is derived from an individual canid (specifically from a population of Native American dogs with coyote contribution),[2][3] it is now essentially living as a unicellular, asexually reproducing (but sexually transmitted) pathogen.[4] Sequence analysis of the genome suggests it diverged from canids over 6,000 years ago; possibly much earlier.[4] Estimates from 2015 date its time of origin to about 11,000 years ago.[5] However, the most recent common ancestor of extant tumors is more recent: it probably originated 200 to 2,500 years ago.[1][6]

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.[7]

Signs and symptoms edit

In male dogs, the tumor affects the penis and foreskin. In female dogs, it affects the vulva. Rarely, the mouth or nose are affected.[8] The tumor often has a cauliflower-like appearance. Signs of genital TVT include a discharge from the prepuce and in some cases urinary retention caused by blockage of the urethra.[9] Signs of a nasal TVT include nasal fistulae, nosebleeds and other nasal discharge, facial swelling, and enlargement of the submandibular lymph nodes.[10]

Pathology edit

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 karyotype 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.[6][11]

Canine transmissible venereal tumors are most commonly seen in sexually active dogs in tropical, subtropical and temperate climates where there are large populations of stray dogs, but little is known about the details of transmission.[12] The disease is spread when dogs mate, and can even be transmitted to other canine species, such as foxes and coyotes.[13] Spontaneous regression of the tumor can occur, probably due to a response from the immune system.[14] CTVT undergoes a predictable cycle: an initial growth phase of four to six months (P phase), a stable phase, and a regression phase (R phase),[15] although not all CTVTs will regress. The tumor does not often metastasize (occurring in about less than 5 percent of cases),[16] except in puppies and immunocompromised dogs. Metastasis occurs to regional lymph nodes,[citation needed] but can also be seen in the skin, brain, eye, liver, spleen, testicle, rectum and muscle.[17] 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 could provide insights for populations that may experience CTVT exposure and information about disease prevalence.[citation needed]

Genetics edit

The CTVT cells have fewer chromosomes than normal dog cells. Dog cells normally have 78 chromosomes, while the cancer cells contain 57–64 chromosomes[7] 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.[9]

All tumor cells of this type of cancer share extremely similar genetic code, often if not always unrelated to the DNA of their host.[6] In addition to the aforementioned c-myc insertion, a few other potential driver mutations have been identified.[18]

Treatment method edit

The tumor, when treated with the chemotherapy drug vincristine, regresses as the host immune system is activated. CCL5 may play an important role in the immune response.[19]

Treatment edit

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.[20] The most common chemotherapy agents used are vincristine, vinblastine, and doxorubicin.[14] Radiotherapy may be required if chemotherapy does not work.[17]

References edit

  1. ^ a b Choi, Charles Q. (2006-08-10). . LiveScience. Archived from the original on 2006-08-20. Retrieved 2006-08-11.
  2. ^ Wang, Xuan; Zhou, Bo-Wen; Yang, Melinda A.; Yin, Ting-Ting; Chen, Fang-Liang; Ommeh, Sheila C.; Esmailizadeh, Ali; Turner, Melissa M.; Poyarkov, Andrei D.; Savolainen, Peter; Wang, Guo-Dong; Fu, Qiaomei; Zhang, Ya-Ping (3 June 2019). "Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to pre-contact dogs in North America". Cell Research. 29 (7): 592–595. bioRxiv 10.1101/350512. doi:10.1038/s41422-019-0183-2. PMC 6796869. PMID 31160719.
  3. ^ Ní Leathlobhair, Máire; Perri, Angela R; Irving-Pease, Evan K; Witt, Kelsey E; Linderholm, Anna; Haile, James; Lebrasseur, Ophelie; Ameen, Carly; Blick, Jeffrey; Boyko, Adam R; Brace, Selina; Cortes, Yahaira Nunes; Crockford, Susan J; Devault, Alison; Dimopoulos, Evangelos A; Eldridge, Morley; Enk, Jacob; Gopalakrishnan, Shyam; Gori, Kevin; Grimes, Vaughan; Guiry, Eric; Hansen, Anders J; Hulme-Beaman, Ardern; Johnson, John; Kitchen, Andrew; Kasparov, Aleksei K; Kwon, Young-Mi; Nikolskiy, Pavel A; Lope, Carlos Peraza; et al. (2018). "The evolutionary history of dogs in the Americas" (PDF). Science. 361 (6397): 81–85. Bibcode:2018Sci...361...81N. doi:10.1126/science.aao4776. PMC 7116273. PMID 29976825.
  4. ^ a b 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.
  5. ^ Strakova, Andrea; Murchison, Elizabeth P (2015). "The cancer which survived: Insights from the genome of an 11000 year-old cancer". Current Opinion in Genetics & Development. 30: 49–55. doi:10.1016/j.gde.2015.03.005. PMID 25867244. S2CID 21195930.
  6. ^ a b c 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.
  7. ^ a b 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.
  8. ^ Morrison, Wallace B. (1998). Cancer in Dogs and Cats (1st ed.). Williams and Wilkins. ISBN 978-0-683-06105-5.
  9. ^ a b Hasler A, Weber W (2000). "Theriogenology question of the month. Transmissible venereal tumor (TVT)". J. Am. Vet. Med. Assoc. 216 (10): 1557–9. doi:10.2460/javma.2000.216.1557. PMID 10825939.
  10. ^ 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, Series A. 48 (7): 391–400. doi:10.1046/j.1439-0442.2001.00361.x. PMID 11599677.
  11. ^ Dingli, D; Nowak, MA (2006). "Cancer biology: infectious tumour cells". Nature. 443 (7107): 35–6. Bibcode:2006Natur.443...35D. doi:10.1038/443035a. PMC 2711443. PMID 16957717.
  12. ^ Vonholdt, B. M; Ostrander, E. A (2006). "The singular history of a canine transmissible tumor". Cell. 126 (3): 445–7. doi:10.1016/j.cell.2006.07.016. PMID 16901777.
  13. ^ 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.
  14. ^ a b 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.
  15. ^ 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.
  16. ^ "Canine Transmissible Venereal Tumor: Introduction". The Merck Veterinary Manual. 2006. Retrieved 2007-04-24.
  17. ^ a b 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. doi:10.5326/15473317-34-6-463. PMID 9826280.
  18. ^ Belov, Katherine; Jones, Elizabeth; Cheng, Yuanyuan (September 2015). "The origin, dynamics, and molecular evolution of transmissible cancers". Advances in Genomics and Genetics: 317. doi:10.2147/AGG.S61298.
  19. ^ Frampton, D; Schwenzer, H; Marino, G; Butcher, LM; Pollara, G; Kriston-Vizi, J; Venturini, C; Austin, R; de Castro, KF; Ketteler, R; Chain, B; Goldstein, RA; Weiss, RA; Beck, S; Fassati, A (9 April 2018). "Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor" (PDF). Cancer Cell. 33 (4): 620–633.e6. doi:10.1016/j.ccell.2018.03.003. PMC 5896242. PMID 29634949.
  20. ^ Ettinger, Stephen J.; Feldman, Edward C. (1995). Textbook of Veterinary Internal Medicine (4th ed.). W.B. Saunders Company. ISBN 978-0-7216-6795-9.

External links edit

  • Transmissible Venereal Tumor from The Pet Health Library
  • Riddle of infectious dog cancer solved at New Scientist
  • Contagious Cancer In Dogs Confirmed; Origins Traced To Wolves Centuries Ago (2006)
  • Dog Cancer Traced Back to Wolf Roots from Nature News

December 07, 2023
canine, transmissible, venereal, tumor, canine, transmissible, venereal, tumor, ctvt, also, known, transmissible, venereal, tumor, canine, transmissible, venereal, sarcoma, ctvs, sticker, tumor, infectious, sarcoma, histiocytic, tumor, external, genitalia, oth. A canine transmissible venereal tumor CTVT also known as a transmissible venereal tumor TVT canine transmissible venereal sarcoma CTVS sticker tumor and infectious sarcoma is a histiocytic tumor of the external genitalia of the dog and other canines and is transmitted from animal to animal during mating It is one of only three known transmissible cancers in mammals the others are devil facial tumor disease a cancer which occurs in Tasmanian devils and contagious reticulum cell sarcoma of the Syrian hamster Illustration of venereal granulomata on a dog s penisThe tumor cells are themselves the infectious agents and the tumors that form are not genetically related to the host dog 1 Although the genome of a CTVT is derived from an individual canid specifically from a population of Native American dogs with coyote contribution 2 3 it is now essentially living as a unicellular asexually reproducing but sexually transmitted pathogen 4 Sequence analysis of the genome suggests it diverged from canids over 6 000 years ago possibly much earlier 4 Estimates from 2015 date its time of origin to about 11 000 years ago 5 However the most recent common ancestor of extant tumors is more recent it probably originated 200 to 2 500 years ago 1 6 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 7 Contents 1 Signs and symptoms 2 Pathology 2 1 Genetics 2 2 Treatment method 3 Treatment 4 References 5 External linksSigns and symptoms editIn male dogs the tumor affects the penis and foreskin In female dogs it affects the vulva Rarely the mouth or nose are affected 8 The tumor often has a cauliflower like appearance Signs of genital TVT include a discharge from the prepuce and in some cases urinary retention caused by blockage of the urethra 9 Signs of a nasal TVT include nasal fistulae nosebleeds and other nasal discharge facial swelling and enlargement of the submandibular lymph nodes 10 Pathology editCanine 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 karyotype 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 6 11 Canine transmissible venereal tumors are most commonly seen in sexually active dogs in tropical subtropical and temperate climates where there are large populations of stray dogs but little is known about the details of transmission 12 The disease is spread when dogs mate and can even be transmitted to other canine species such as foxes and coyotes 13 Spontaneous regression of the tumor can occur probably due to a response from the immune system 14 CTVT undergoes a predictable cycle an initial growth phase of four to six months P phase a stable phase and a regression phase R phase 15 although not all CTVTs will regress The tumor does not often metastasize occurring in about less than 5 percent of cases 16 except in puppies and immunocompromised dogs Metastasis occurs to regional lymph nodes citation needed but can also be seen in the skin brain eye liver spleen testicle rectum and muscle 17 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 could provide insights for populations that may experience CTVT exposure and information about disease prevalence citation needed Genetics edit The CTVT cells have fewer chromosomes than normal dog cells Dog cells normally have 78 chromosomes while the cancer cells contain 57 64 chromosomes 7 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 9 All tumor cells of this type of cancer share extremely similar genetic code often if not always unrelated to the DNA of their host 6 In addition to the aforementioned c myc insertion a few other potential driver mutations have been identified 18 Treatment method edit The tumor when treated with the chemotherapy drug vincristine regresses as the host immune system is activated CCL5 may play an important role in the immune response 19 Treatment editSurgery 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 20 The most common chemotherapy agents used are vincristine vinblastine and doxorubicin 14 Radiotherapy may be required if chemotherapy does not work 17 References edit a b Choi Charles Q 2006 08 10 Contagious Canine Cancer Spread by Parasites LiveScience Archived from the original on 2006 08 20 Retrieved 2006 08 11 Wang Xuan Zhou Bo Wen Yang Melinda A Yin Ting Ting Chen Fang Liang Ommeh Sheila C Esmailizadeh Ali Turner Melissa M Poyarkov Andrei D Savolainen Peter Wang Guo Dong Fu Qiaomei Zhang Ya Ping 3 June 2019 Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to pre contact dogs in North America Cell Research 29 7 592 595 bioRxiv 10 1101 350512 doi 10 1038 s41422 019 0183 2 PMC 6796869 PMID 31160719 Ni Leathlobhair Maire Perri Angela R Irving Pease Evan K Witt Kelsey E Linderholm Anna Haile James Lebrasseur Ophelie Ameen Carly Blick Jeffrey Boyko Adam R Brace Selina Cortes Yahaira Nunes Crockford Susan J Devault Alison Dimopoulos Evangelos A Eldridge Morley Enk Jacob Gopalakrishnan Shyam Gori Kevin Grimes Vaughan Guiry Eric Hansen Anders J Hulme Beaman Ardern Johnson John Kitchen Andrew Kasparov Aleksei K Kwon Young Mi Nikolskiy Pavel A Lope Carlos Peraza et al 2018 The evolutionary history of dogs in the Americas PDF Science 361 6397 81 85 Bibcode 2018Sci 361 81N doi 10 1126 science aao4776 PMC 7116273 PMID 29976825 a b 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 Andrea Murchison Elizabeth P 2015 The cancer which survived Insights from the genome of an 11000 year old cancer Current Opinion in Genetics amp Development 30 49 55 doi 10 1016 j gde 2015 03 005 PMID 25867244 S2CID 21195930 a b c 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 a b 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 Morrison Wallace B 1998 Cancer in Dogs and Cats 1st ed Williams and Wilkins ISBN 978 0 683 06105 5 a b Hasler A Weber W 2000 Theriogenology question of the month Transmissible venereal tumor TVT J Am Vet Med Assoc 216 10 1557 9 doi 10 2460 javma 2000 216 1557 PMID 10825939 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 Series A 48 7 391 400 doi 10 1046 j 1439 0442 2001 00361 x PMID 11599677 Dingli D Nowak MA 2006 Cancer biology infectious tumour cells Nature 443 7107 35 6 Bibcode 2006Natur 443 35D doi 10 1038 443035a PMC 2711443 PMID 16957717 Vonholdt B M Ostrander E A 2006 The singular history of a canine transmissible tumor Cell 126 3 445 7 doi 10 1016 j cell 2006 07 016 PMID 16901777 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 a b 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 a b 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 doi 10 5326 15473317 34 6 463 PMID 9826280 Belov Katherine Jones Elizabeth Cheng Yuanyuan September 2015 The origin dynamics and molecular evolution of transmissible cancers Advances in Genomics and Genetics 317 doi 10 2147 AGG S61298 Frampton D Schwenzer H Marino G Butcher LM Pollara G Kriston Vizi J Venturini C Austin R de Castro KF Ketteler R Chain B Goldstein RA Weiss RA Beck S Fassati A 9 April 2018 Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor PDF Cancer Cell 33 4 620 633 e6 doi 10 1016 j ccell 2018 03 003 PMC 5896242 PMID 29634949 Ettinger Stephen J Feldman Edward C 1995 Textbook of Veterinary Internal Medicine 4th ed W B Saunders Company ISBN 978 0 7216 6795 9 External links editTransmissible Venereal Tumor from The Pet Health Library Riddle of infectious dog cancer solved at New Scientist Contagious Cancer In Dogs Confirmed Origins Traced To Wolves Centuries Ago 2006 Dog Cancer Traced Back to Wolf Roots from Nature News Retrieved from https en wikipedia org w index php title Canine transmissible venereal tumor amp oldid 1186049589, wikipedia, wiki, book, books, library,

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