Melanoma is a type of cancer that occurs commonly
in dogs with pigmented (dark) skin. Melanomas can occur in areas
of haired skin, where they usually form small, dark (brown to black) lumps,
but can also appear as large, flat, wrinkled masses. Melanomas also
can occur in the mouth, toes, or behind the eye. In general, skin
melanomas tend to be benign, and those in the mouth, toes, or eyes tend
to be malignant. However, there are many exceptions to this rule.
The term cancer
refers to a large number of diseases whose only common feature is uncontrolled
cell growth and proliferation (multiplication). This loss of cell
growth control results from an accumulation of mutations
(errors introduced into the DNA code) in genes that control cell division
and cell survival.
The most common mechanism
that introduces mutations into the DNA of somatic cells (non-reproductive
cells) is the inherent error that occurs during normal cell division.
In mammalian cells, there is an error rate of about 1 in 1,000,000 to 1
in 10,000,000 bases during each round of replication. The genome
consists of many millions of base pairs, so each daughter cell is likely
to carry at least a few mutations in its DNA. Most of these mutations
are silent; that is, they do not present any problems to the cell’s ability
to function. However, others can disable tumor suppressor
genes or activate oncogenes that respectively
inhibit or promote cell division and survival. Given the fact that
cell division is responsible for most mutations, it is not surprising that
the most common cancers arise from cells that divide frequently in the
performance of their function.
Fortunately, the body has
many built-in safeguards that mandate that abnormal cells be destroyed.
For that reason, before cancer can take hold, a malignant cell must eliminate
or evade these safeguards. The reliability of these systems is evident
in the fact that our pets are not “walking tumors”. Still, cancer
is the most frequent cause of death in dogs.
Melanoma arises from melanocytes,
cells that impart pigment or coloration to the skin. In humans, melanoma
arises due to mutations induced by repeated, intense exposure to ultraviolet
light (for example, frequent tanning or working outdoors). This does
not seem to be a major factor in dogs, as in most breeds the hair coat
affords them protection from sunlight. However, pigment cells divide
every time there is injury to the skin, or if there is constant trauma
(for example, areas where dogs constantly scratch or lick). Nevertheless,
risk factors for canine melanoma are not well established.
Mutations that contribute
to cancer can also be inherited. An inherited mutation in a single
gene that is important in cell growth control will increase the risk of
that individual to develop cancer. This can be due to reducing the
overall number of acquired mutations that must accumulate before a cell
becomes cancerous, or it can be due to disabling a critical safeguard gene
that normally prevents cells from becoming tumors. Specific genes
that are responsible for familial melanoma have been identified in humans
and in mice. In dogs, there appears to be a predisposition among
certain breeds or families to develop specific types of cancer, suggesting
that a hereditary component may be important in the development or progression
of the disease.
The laboratory of Dr. Jaime
Modiano at the AMC Cancer Center has an ongoing program to define the role
of genetics in canine cancer. With support from the Canine Health
Foundation of the American Kennel Club and specific breed clubs, Dr. Modiano
is evaluating the role of various target genes in canine melanoma.
For additional information on this project, or to inquire if your breed
can be included in Dr. Modiano’s study we encourage you to visit the CHF
web site at http://www.akcchf.org/,
or contact your breed club’s health representative.
By Jaime F. Modiano, Ph.D.
Dr. Modiano completed his veterinary training
and PhD in Immunology at the University of Pennsylvania, a residency in
Veterinary Clinical Pathology at Colorado State University, and a post-doctoral
fellowship at the National Jewish Center for Immunology and Respiratory
Medicine. He was appointed to the faculty in the Department of Veterinary
Pathobiology at Texas A&M University as Assistant Professor between
1995 and 1999. Currently, Dr. Modiano is a scientist in the Center
for Cancer Causation and Prevention at the AMC Cancer Research Center in
Denver, Colorado, and a Full Member of the Comprehensive Cancer Center
of the University of Colorado Health Sciences Center. His work is
supported through federal and private sources, including the following
grant from the AKC Canine Health Foundation:
No. 1626: Significance of Tumor Suppressor Genes in Canine Cancer