Clues to melanoma treatments lie in profiles of disease subtypes

Key Points

Banff, Alberta - The identification of genetic mutations in melanoma has opened the door to targeted treatment of melanomas.

"What we have been doing over the years is breaking down melanoma into distinct categories and generating evidence that there are biologically distinct subtypes, and they all have their own genetic alterations that happen early during progression," Dr. Bastian says.

As perhaps the most striking example, he states melanomas of the eye, which arise through mutations in distinct genes, compared to melanomas that originate on the skin.

Examining BRAF

Dr. Bastian says melanomas of the skin that arise due to BRAF mutations are another example of a distinct subtype. This melanoma occurs comparatively early in life and does not require large cumulative doses of ultraviolet light. These melanomas account for approximately 60 percent of all melanomas in people from European descent. These melanomas tend to occur on the trunk and proximal extremities and are less likely to occur on the head and neck.

"They predominantly affect individuals with many moles and tend to arise relatively early in life," Dr. Bastian says. "The nevi arise in the first two decades, and the melanomas occur in the following decades after the age of 50."

Dr. Bastian stresses that BRAF mutations in and of themselves are not sufficient to cause melanomas. "There are growth-suppressing mechanisms that these cells possess, and these have to be overridden by the acquisition of additional genetic alterations," he says. The tumor-suppressor mechanisms are quite robust, Dr. Bastian says.

The presence of multiple nevi, most of which also harbor BRAF mutations, indicates individuals who are highly susceptible to developing BRAF mutations.

"The fact that they develop these mutations early in life suggests that there is a particular window of vulnerability for these individuals to develop these mutations," he says. "This has been shown in many epidemiological studies. We don't know what the basis of the window is, but it seems to exist."

It would be regarded a considerable risk for these individuals to either visit tanning salons or go to the beach to tan, especially early in life, Dr. Bastian says.