Scientists discover how ultraviolet rays trigger skin cancer. They may also have found a way to stop skin cancer in its tracks using a gene target.
Melanoma is a cancer of the skin pigment cells, which are called melanocytes. Melanoma only accounts for around 1 percent of all skin cancers, yet it is responsible for most skin cancer-related deaths.
Melanomas can occur anywhere on the skin, but they are most likely to develop on the chest and back in men and on the legs in women. Other common sites for melanomas include the neck and face.
In the United States, around 87,110 new cases of melanoma will be diagnosed in 2017, according to the American Cancer Society (ACS). They also estimate that around 9,730 individuals will die from the disease.
Although some of these melanoma cases stem from pre-existing moles, most come from sources that were, until now, unknown.
New research, led by Andrew White — an assistant professor of biomedical sciences at Cornell University's College of Veterinary Medicine in Ithaca, NY — has found that when melanocyte stem cells accumulate a certain number of genetic mutations, they become potential cancer-causing cells.
The study findings were published in the journal Cell Stem Cell.
When exposed to ultraviolet (UV) radiation, melanocytes release melanin, a dark brown to black pigment that protects the skin from the sun's rays. But in melanocyte stem cells that have reached and exceeded a threshold of genetic mutations, activation by sun exposure causes them to grow a tumor.
"If you had mutations that were sufficient for melanoma, everything would be fine until you went out and got a sunburn," says Prof. White. "The stimuli that would normally just give you a tanning response could, in fact, start a melanoma instead."
He and his colleagues also reveal that they may have identified a way to prevent melanomas that are caused by the mutated stem cells.
Mice with gene deletion remained healthy
The researchers hypothesized that a gene called Hgma2 is expressed in the skin when exposed to UV radiation. When Hgma2 is expressed, it enables melanocyte stem cells to shift from where they are situated at the base of the hair follicles to the surface of the skin, or the epidermis, where they release melanin.
The team used two sets of mice that were engineered to have melanocyte stem cell mutations to test Hgma2's role in the development of melanomas. One group of mice had only the mutations, while the other group had mutations and the Hgma2 gene deleted.
All the mice were given a dose of UV radiation just high enough to stimulate a "tanning response."
The mice that had the stem cell mutations and an intact Hgma2 gene developed melanomas, while the mice with the mutations and the deleted Hgma2 gene stayed healthy.
"We have an actual mechanism, with Hgma2, that can be explored in the future and could be a way we can prevent melanomas from happening."
Prof. Andrew White
Although the findings are promising, the researchers note that more studies need to be completed to improve our understanding of the Hgma2 gene.