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Many risk factors for melanoma have been found, but it’s not always clear exactly how they might cause cancer.

For example, while most moles never turn into a melanoma, some do. Researchers have found some gene changes inside mole cells that may cause them to become melanoma cells. But it’s still not known exactly why some moles become cancerous while most don’t.

DNA is the chemical in each of our cells that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when our cells grow, divide into new cells, and die:

  • Genes that help cells grow, divide, and stay alive are called oncogenes.
  • Genes that keep cell growth in check or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become a cancer cell.

Ultraviolet (UV) rays are clearly a major cause of melanoma. UV rays can damage the DNA in skin cells. Sometimes this damage affects certain genes that control how skin cells grow and divide. If these genes no longer work properly, the affected cells may become cancer cells.

Most UV rays come from sunlight, but some can come from man-made sources such as tanning beds. Usually it’s not clear exactly when the DNA damage from UV exposure occurs. Some of the damage may take place in the few years before the cancer appears. But much of it may be from exposures that happened many years earlier. Children and young adults often get a lot of intense sun exposure that might not result in cancer until many years or even decades later.

Most of the gene changes commonly seen in melanoma cells are not inherited. They are more likely the result of damage caused by sunlight. In some people, such as those with xeroderma pigmentosum (XP), the skin cells are not as able to repair damaged DNA. These people are more likely to develop melanoma.

Some melanomas occur in parts of the body that are rarely exposed to sunlight. These melanomas often have different gene changes than those in melanomas that develop in sun-exposed areas.

When melanomas run in families, gene changes (mutations) that greatly increase the risk of melanoma are often passed from one generation to the next. Familial (inherited) melanomas most often have changes in tumor suppressor genes such as CDKN2A (also known as p16) and CDK4 that prevent them from doing their normal job of controlling cell growth. This could eventually lead to cancer.

Many other gene changes have been found in melanoma cells as well. Some of these have proven to be good targets for drugs to help treat this disease. For example, about half of all melanomas have a change in the BRAF oncogene that helps drive their growth. This change is not inherited. It seems to occur during the development of the melanoma. Several drugs that specifically target cells with this gene change are now used to treat these melanomas (see Targeted therapy for melanoma skin cancer).

Last Medical Review: 05/19/2016
Last Revised: 05/20/2016