Canine transmissible venereal tumor
Encyclopedia
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
of the dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
and other canids that mainly affects the external genitalia, and is transmitted from animal to animal during copulation. It is one of only three known transmissible cancers; another is Devil facial tumor disease, a cancer which occurs in Tasmanian devils
Tasmanian Devil
The Tasmanian devil is a carnivorous marsupial of the family Dasyuridae, now found in the wild only on the Australian island state of Tasmania. The size of a small dog, it became the largest carnivorous marsupial in the world following the extinction of the thylacine in 1936...
.
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 CTVT is derived from a canid (probably a dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
, wolf or coyote
Coyote
The coyote , also known as the American jackal or the prairie wolf, is a species of canine found throughout North and Central America, ranging from Panama in the south, north through Mexico, the United States and Canada...
), 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. However, the most recent common ancestor
Most recent common ancestor
In genetics, the most recent common ancestor of any set of organisms is the most recent individual from which all organisms in the group are directly descended...
of extant tumors is more recent: it probably originated 200 to 2,500 years ago.
Canine TVT was initially described by Russian veterinarian
Veterinarian
A veterinary physician, colloquially called a vet, shortened from veterinarian or veterinary surgeon , is a professional who treats disease, disorder and injury in animals....
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.
Biology
CTVT is a histiocytic tumorTumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
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, CTVT 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 CTVT.
CTVT cells have fewer chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s than normal cells. Dog cells normally have 78 chromosomes; CTVT tumor cells contain 57–64 chromosomes that are very different in appearance from normal dog chromosomes. All dog chromosomes except X
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
and Y
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
are acrocentric, having a centromere
Centromere
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come closest in contact. It is involved in cell division as the point of mitotic spindle attachment...
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
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
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
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
of their host. Specifically, the LINE-1 (Long interspersed nuclear element) 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.
CTVT is most commonly seen in sexually active dogs in tropical
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately N and the Tropic of Capricorn in the southern hemisphere at S; these latitudes correspond to the axial tilt of the Earth...
and subtropical
Subtropics
The subtropics are the geographical and climatical zone of the Earth immediately north and south of the tropical zone, which is bounded by the Tropic of Cancer and the Tropic of Capricorn, at latitudes 23.5°N and 23.5°S...
climates. The disease is spread when dogs mate, and it can even be transmitted to other canine species, such as fox
Fox
Fox is a common name for many species of omnivorous mammals belonging to the Canidae family. Foxes are small to medium-sized canids , characterized by possessing a long narrow snout, and a bushy tail .Members of about 37 species are referred to as foxes, of which only 12 species actually belong to...
es and coyote
Coyote
The coyote , also known as the American jackal or the prairie wolf, is a species of canine found throughout North and Central America, ranging from Panama in the south, north through Mexico, the United States and Canada...
s. Spontaneous regression of the tumor can occur, probably due to a response from the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. 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
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
(occurring in about 5 percent of cases), except in puppies and immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
dogs. Metastasis is most commonly to regional lymph nodes, but can also be seen in the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, eye
Eye
Eyes are organs that detect light and convert it into electro-chemical impulses in neurons. The simplest photoreceptors in conscious vision connect light to movement...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, testicle
Testicle
The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
, and muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
. Biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
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, CTVT takes advantage of the popular sire effect
Popular sire effect
The Popular sire effect occurs when a show dog with desirable physical attributes is bred repeatedly. This can cause unknown undesirable genetic traits in the stud to spread rapidly within the gene pool. It can also reduce genetic diversity by the exclusion of other males...
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 CTVT will provide insights for populations that may experience CTVT exposure and
information about disease prevalence. CTVT is 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 penisPenis
The penis is a biological feature of male animals including both vertebrates and invertebrates...
or prepuce
Foreskin
In male human anatomy, the foreskin is a generally retractable double-layered fold of skin and mucous membrane that covers the glans penis and protects the urinary meatus when the penis is not erect...
. In females, it affects the vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
or labia. Rarely, the mouth or nose are affected. The tumor often has a cauliflower
Cauliflower
Cauliflower is one of several vegetables in the species Brassica oleracea, in the family Brassicaceae. It is an annual plant that reproduces by seed...
-like appearance. Signs of genital TVT include a discharge from the prepuce and in some cases urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, from blockage of the urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
. Signs of nasal TVT include orinasal fistula
Fistula
In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
e, nosebleed
Nosebleed
Epistaxis or a nosebleed is the relatively common occurrence of hemorrhage from the nose, usually noticed when the blood drains out through the nostrils...
s and other nasal discharge, facial swelling, and enlargement of the submandibular lymph nodes.
Treatment
ChemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is very effective for TVT, but surgery alone often leads to recurrence. Surgery may be difficult due to the location of these tumors. The prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
for complete remission with chemotherapy is excellent. The most common chemotherapy agents used for TVT are vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
, vinblastine
Vinblastine
Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....
, and doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
. Radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
may be effective when chemotherapy does not work.
External links
- Transmissible Venereal Tumor from The Pet Health Library
- IVIS — http://www.ivis.org/docarchive/A1233.0405.pdf
- 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 LondonUniversity College LondonUniversity College London is a public research university located in London, United Kingdom and the oldest and largest constituent college of the federal University of 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.