Title: Canine transmissible venereal tumor

{{short description|Disease in dogs and other canines}}
[[File:Surgical diseases and surgery of the dog (1906) (14784705963).jpg|thumb|Venereal granulomata on a dog's penis]]
A '''canine transmissible venereal tumor''' ('''CTVT'''), also known as a '''transmissible venereal tumor''' ('''TVT'''), '''canine transmissible venereal sarcoma''' ('''CTVS'''), '''sticker tumor''' or '''infectious sarcoma''', is a [[histiocytic]] [[tumor]] of [[Canine reproduction#Canine sexual anatomy and development|the external genitalia of the dog]] and other canines, and is transmitted from animal to animal during [[sexual behavior of dogs|mating]].&lt;ref&gt;{{Cite journal |last=Murchison |first=E P |date=December 2008 |title=Clonally transmissible cancers in dogs and Tasmanian devils |url=https://www.nature.com/articles/onc2009350 |journal=Oncogene |language=en |volume=27 |issue=S2 |pages=S19–S30 |doi=10.1038/onc.2009.350 |pmid=19956175 |issn=0950-9232|url-access=subscription }}&lt;/ref&gt;&lt;ref&gt;{{Cite journal |last1=Ní Leathlobhair |first1=Máire |last2=Lenski |first2=Richard E. |date=2022-07-25 |title=Population genetics of clonally transmissible cancers |url=https://www.nature.com/articles/s41559-022-01790-3 |journal=Nature Ecology &amp; Evolution |language=en |volume=6 |issue=8 |pages=1077–1089 |doi=10.1038/s41559-022-01790-3 |pmid=35879542 |bibcode=2022NatEE...6.1077N |issn=2397-334X}}&lt;/ref&gt; It is one of only three known [[transmissible cancer]]s in [[mammal]]s; the others are [[devil facial tumor disease]], a cancer which occurs in [[Tasmanian devil]]s, and [[contagious reticulum cell sarcoma]] of the [[Syrian hamster]].

The tumor cells are themselves the infectious agents, and the tumors that form are not genetically related to the host dog.&lt;ref name=&quot;livescience&quot; /&gt; Although the genome of a CTVT is derived from an individual [[canid]] (specifically from a population of [[Native American dogs]] with coyote contribution),&lt;ref&gt;{{cite journal |last1=Wang |first1=Xuan |last2=Zhou |first2=Bo-Wen |last3=Yang |first3=Melinda A. |last4=Yin |first4=Ting-Ting |last5=Chen |first5=Fang-Liang |last6=Ommeh |first6=Sheila C. |last7=Esmailizadeh |first7=Ali |last8=Turner |first8=Melissa M. |last9=Poyarkov |first9=Andrei D. |last10=Savolainen |first10=Peter |last11=Wang |first11=Guo-Dong |last12=Fu |first12=Qiaomei |last13=Zhang |first13=Ya-Ping |title=Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to pre-contact dogs in North America |journal=Cell Research |date=3 June 2019 |volume=29 |issue=7 |pages=592–595 |doi=10.1038/s41422-019-0183-2|pmid=31160719 |pmc=6796869 |biorxiv=10.1101/350512 |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite journal|doi=10.1126/science.aao4776|pmid=29976825|title=The evolutionary history of dogs in the Americas|journal=Science|volume=361|issue=6397|pages=81–85|year=2018|last1=Ní Leathlobhair|first1=Máire|last2=Perri|first2=Angela R|last3=Irving-Pease|first3=Evan K|last4=Witt|first4=Kelsey E|last5=Linderholm|first5=Anna|last6=Haile|first6=James|last7=Lebrasseur|first7=Ophelie|last8=Ameen|first8=Carly|last9=Blick|first9=Jeffrey|last10=Boyko|first10=Adam R|last11=Brace|first11=Selina|last12=Cortes|first12=Yahaira Nunes|last13=Crockford|first13=Susan J|last14=Devault|first14=Alison|last15=Dimopoulos|first15=Evangelos A|last16=Eldridge|first16=Morley|last17=Enk|first17=Jacob|last18=Gopalakrishnan|first18=Shyam|last19=Gori|first19=Kevin|last20=Grimes|first20=Vaughan|last21=Guiry|first21=Eric|last22=Hansen|first22=Anders J|last23=Hulme-Beaman|first23=Ardern|last24=Johnson|first24=John|last25=Kitchen|first25=Andrew|last26=Kasparov|first26=Aleksei K|last27=Kwon|first27=Young-Mi|last28=Nikolskiy|first28=Pavel A|last29=Lope|first29=Carlos Peraza|last30=Manin|first30=Aurélie|pmc=7116273|bibcode=2018Sci...361...81N|display-authors=29|url=http://dro.dur.ac.uk/25675/1/25675.pdf|doi-access=free}}&lt;/ref&gt; it is now essentially living as a unicellular, asexually reproducing (but [[sexually transmitted disease|sexually transmitted]]) [[pathogen]].&lt;ref name=&quot;rebbeck&quot;&gt;{{cite journal|vauthors=Rebbeck CA, Thomas R, Breen M, Leroi AM, Burt A|year=2009|title=Origins and Evolution of a Transmissible Cancer|journal=Evolution|volume=63|issue=9|pages=2340–2349|doi=10.1111/j.1558-5646.2009.00724.x|pmid=19453727|doi-access=free}}&lt;/ref&gt; Sequence analysis of the genome suggests it diverged over 6,000 years ago; possibly much earlier.&lt;ref name=&quot;rebbeck&quot; /&gt; Estimates from 2015 date its time of origin to about 11,000 years ago.&lt;ref name=Strakova2015&gt;{{Cite journal|doi=10.1016/j.gde.2015.03.005|pmid=25867244|title=The cancer which survived: Insights from the genome of an 11000 year-old cancer|journal=Current Opinion in Genetics &amp; Development|volume=30|pages=49–55|year=2015|last1=Strakova|first1=Andrea|last2=Murchison|first2=Elizabeth P|s2cid=21195930 |url=https://www.repository.cam.ac.uk/handle/1810/247911}}&lt;/ref&gt; However, the [[most recent common ancestor]] of ''extant'' tumors is more recent: it probably originated 200 to 2,500 years ago.&lt;ref name=&quot;livescience&quot;&gt;{{cite web|url=http://www.livescience.com/animalworld/060810_dog_cancer.html|title=Contagious Canine Cancer Spread by Parasites|last=Choi|first=Charles Q.|date=2006-08-10|publisher=LiveScience|url-status=dead|archive-url=https://web.archive.org/web/20060820191525/http://www.livescience.com/animalworld/060810_dog_cancer.html|archive-date=2006-08-20|accessdate=2006-08-11}}&lt;/ref&gt;&lt;ref name=&quot;Murgia_2006&quot;&gt;{{cite journal|last=Murgia|first=C|author2=Pritchard JK|author2-link=Jonathan K. Pritchard|author3=Kim SY|author4=Fassati A|author5=Weiss RA|title=Clonal Origin and Evolution of a Transmissible Cancer|journal=Cell|volume=126|issue=3|pages=477–87|date=2006-08-11|pmid=16901782|doi=10.1016/j.cell.2006.05.051|pmc=2593932}}&lt;/ref&gt;

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.&lt;ref name=Martins_2005&gt;{{cite web|last1=Mello Martins|first1=M.I.|last2=de Souza|first2=F. Ferreira|last3=Gobello|first3=C.|year=2005|title=Canine transmissible venereal tumor: Etiology, pathology, diagnosis and treatment|website=Recent Advances in Small Animal Reproduction|url=http://www.ivis.org/advances/Concannon/gobello2/chapter.asp?LA=1|accessdate=2006-05-25}}&lt;/ref&gt;

==Signs and symptoms==
In male [[dogs]], the tumor affects the [[Dog penis|penis]] and [[Penile sheath|sheath]]. In female dogs, it affects the [[vulva]]. Rarely, the mouth or nose are affected.&lt;ref name=Morrison_1998&gt;{{cite book|last=Morrison|first=Wallace B.|title=Cancer in Dogs and Cats|edition=1st|publisher=Williams and Wilkins|year=1998|isbn=978-0-683-06105-5}}&lt;/ref&gt; 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]].&lt;ref name=Hasler/&gt; Signs of a nasal TVT include nasal [[fistula]]e, [[nosebleed]]s and other nasal discharge, facial [[swelling (medical)|swelling]], and enlargement of the submandibular [[lymph nodes]].&lt;ref&gt;{{cite journal|vauthors=Papazoglou L, Koutinas A, Plevraki A, Tontis D|title=Primary intranasal transmissible venereal tumour in the dog: a retrospective study of six spontaneous cases|journal=Journal of Veterinary Medicine, Series A|volume=48|issue=7|pages=391–400|year=2001|pmid=11599677|doi=10.1046/j.1439-0442.2001.00361.x}}&lt;/ref&gt;

==Pathology==
Canine transmissible venereal tumors are [[histiocytic]] [[tumor]]s that may be transmitted among dogs through [[canine tying|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 [[chromosome]]s in all tumors collected in different geographic regions. Third, a [[long interspersed nuclear element]] (LINE-1) insertion near the [[Myc|c-myc]] gene 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.&lt;ref name=&quot;Murgia_2006&quot; /&gt;&lt;ref&gt;{{cite journal|last1=Dingli|first1=D|last2=Nowak|first2=MA|year=2006|title=Cancer biology: infectious tumour cells|journal=Nature|volume=443|issue=7107|pages=35–6|doi=10.1038/443035a|pmid=16957717|pmc=2711443|bibcode=2006Natur.443...35D}}&lt;/ref&gt;

Canine transmissible venereal tumors are most commonly seen in sexually active dogs in [[Tropics|tropical]], [[Subtropics|subtropical]] and temperate climates where there are large populations of stray dogs, but little is known about the details of transmission.&lt;ref&gt;{{cite journal|pmid=16901777|year=2006|last1=Vonholdt|first1=B. M|title=The singular history of a canine transmissible tumor|journal=Cell|volume=126|issue=3|pages=445–7|last2=Ostrander|first2=E. A|doi=10.1016/j.cell.2006.07.016|doi-access=free}}&lt;/ref&gt; The disease is spread when dogs mate, and can even be transmitted to [[Canidae|other canine species]], such as [[fox]]es and coyotes.&lt;ref&gt;{{cite journal|vauthors=Mukaratirwa S, Gruys E|title=Canine transmissible venereal tumour: cytogenetic origin, immunophenotype, and immunobiology. A review|journal=The Veterinary Quarterly|volume=25|issue=3|pages=101–11|year=2003|pmid=14535580|doi=10.1080/01652176.2003.9695151|doi-access=free}}&lt;/ref&gt; Spontaneous regression of the tumor can occur, probably due to a response from the [[immune system]].&lt;ref name=Stettner&gt;{{cite journal|vauthors=Stettner N, Brenner O, Eilam R, Harmelin A|title=Pegylated liposomal doxorubicin as a chemotherapeutic agent for treatment of canine transmissible venereal tumor in murine models|journal=J. Vet. Med. Sci.|volume=67|issue=11|pages=1133–9|year=2005|pmid=16327225|doi=10.1292/jvms.67.1133|doi-access=free}}&lt;/ref&gt; 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),&lt;ref&gt;{{cite journal|vauthors=Liao K, Hung S, Hsiao Y, Bennett M, Chu R|title=Canine transmissible venereal tumor cell depletion of B lymphocytes: molecule(s) specifically toxic for B cells|journal=Vet. Immunol. Immunopathol.|volume=92|issue=3–4|pages=149–62|year=2003|pmid=12730015|doi=10.1016/S0165-2427(03)00032-1}}&lt;/ref&gt; although not all CTVTs will regress. The tumor does not often [[metastasis|metastasize]] (occurring in about less than 5 percent of cases),&lt;ref&gt;{{cite web|title=Canine Transmissible Venereal Tumor: Introduction|website=The Merck Veterinary Manual|date=2006|url=http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/112500.htm|accessdate=2007-04-24|archive-date=2015-06-09|archive-url=https://web.archive.org/web/20150609030026/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/112500.htm|url-status=dead}}&lt;/ref&gt; except in puppies and [[Immunodeficiency|immunocompromised]] dogs. Metastasis occurs to regional [[lymph nodes]],{{cn|date=May 2024}} but can also be seen in the [[skin]], [[brain]], [[eye]], [[liver]], [[spleen]], [[testicle]], rectum and [[muscle]].&lt;ref name=&quot;Rogers&quot;&gt;{{cite journal|vauthors=Rogers K, Walker M, Dillon H|title=Transmissible venereal tumor: a retrospective study of 29 cases|journal=[[Journal of the American Animal Hospital Association]]|volume=34|issue=6|pages=463–70|year=1998|pmid=9826280|doi=10.5326/15473317-34-6-463}}&lt;/ref&gt; 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.{{cn|date=January 2023}}

=== Genetics ===
The CTVT cells have fewer [[chromosome]]s than normal dog cells. Dog cells normally have 78 chromosomes, while the cancer cells contain 57–64 chromosomes&lt;ref name=Martins_2005/&gt; that are very different in appearance from normal dog chromosomes. All dog chromosomes except [[X chromosome|X]] and [[Y chromosome|Y]] are [[acrocentric chromosome|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.&lt;ref name=Hasler&gt;{{cite journal|vauthors=Hasler A, Weber W|title=Theriogenology question of the month. Transmissible venereal tumor (TVT)|journal=J. Am. Vet. Med. Assoc.|volume=216|issue=10|pages=1557–9|year=2000|doi=10.2460/javma.2000.216.1557|pmid=10825939|doi-access=free}}&lt;/ref&gt;

All tumor cells of this type of cancer share extremely similar genetic code, often if not always unrelated to the [[DNA]] of their host.&lt;ref name=&quot;Murgia_2006&quot; /&gt; In addition to the aforementioned c-myc insertion, a few other potential [[Somatic evolution in cancer#Glossary|driver mutation]]s have been identified.&lt;ref&gt;{{cite journal |last1=Belov |first1=Katherine |last2=Jones |first2=Elizabeth |last3=Cheng |first3=Yuanyuan |title=The origin, dynamics, and molecular evolution of transmissible cancers |journal=Advances in Genomics and Genetics |date=September 2015 |pages=317 |doi=10.2147/AGG.S61298|doi-access=free }}&lt;/ref&gt;

===Treatment method===
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.&lt;ref&gt;{{cite journal|last1=Frampton|first1=D|last2=Schwenzer|first2=H|last3=Marino|first3=G|last4=Butcher|first4=LM|last5=Pollara|first5=G|last6=Kriston-Vizi|first6=J|last7=Venturini|first7=C|last8=Austin|first8=R|last9=de Castro|first9=KF|last10=Ketteler|first10=R|last11=Chain|first11=B|last12=Goldstein|first12=RA|last13=Weiss|first13=RA|last14=Beck|first14=S|last15=Fassati|first15=A|title=Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.|journal=Cancer Cell|date=9 April 2018|volume=33|issue=4|pages=620–633.e6|doi=10.1016/j.ccell.2018.03.003|pmid=29634949|url=http://discovery.ucl.ac.uk/10046739/1/PIIS1535610818300710.pdf|pmc=5896242}}&lt;/ref&gt;

==Treatment==
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 (medicine)|remission]] with chemotherapy is excellent.&lt;ref name=Ettinger_1995&gt;{{cite book|last1=Ettinger|first1=Stephen J.|last2=Feldman|first2=Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=978-0-7216-6795-9}}&lt;/ref&gt; The most common chemotherapy agents used are [[vincristine]], [[vinblastine]], and [[doxorubicin]].&lt;ref name=Stettner/&gt;  Use of [[autohaemotherapy]] in treatment of TVTs also showed promising results in many cases.&lt;ref&gt;{{Cite journal |last1=Arif |first1=S. A. |last2=Das |first2=T. |last3=Deka |first3=D. |last4=Kachari |first4=J. |last5=Barman |first5=U. |last6=Changkija |first6=B. |last7=Patgiri |first7=D. |date=2023-10-28 |title=Management of canine transmissible venereal tumour using autohaemotherapy: A vpromising approach |url=https://www.ijah.in/upload/snippet/31(172-22)-SC.pdf |journal=Indian Journal of Animal Health |volume=Online |doi=10.36062/ijah.2023.17222}}&lt;/ref&gt; [[Radiation therapy|Radiotherapy]] may be required if chemotherapy does not work.&lt;ref name=Rogers/&gt;

==References==
{{Reflist}}

==External links==
* [https://veterinarypartner.vin.com/default.aspx?pid=19239&amp;id=4952049 Transmissible Venereal Tumor] from The Pet Health Library
* [https://www.newscientist.com/article/dn9713-riddle-of-infectious-dog-cancer-solved/ Riddle of infectious dog cancer solved] at ''[[New Scientist]]''
* [https://www.sciencedaily.com/releases/2006/08/060811075902.htm Contagious Cancer In Dogs Confirmed; Origins Traced To Wolves Centuries Ago] (2006)
* [https://www.nature.com/articles/news060807-13 Dog Cancer Traced Back to Wolf Roots] from ''[[Nature News]]''

[[Category:Cancer in dogs|Transmissible venereal tumor]]
[[Category:Types of animal cancers]]
[[Category:Clonally transmissible cancers]]
[[Category:Sexually transmitted diseases and infections]]