Malignant Melanoma and the CDKN2A gene

Malignant Melanoma and the CDKN2A gene

In Australia, melanoma is the 3rd most common cancer. It affects 1:18 people, mainly over age 60.

When 2 or more first degree relatives (close relatives such as your parents, brothers and sisters or children) have had a melanoma, it is referred to as Familial Malignant Melanoma syndrome.

Increased risk of melanoma can be caused by genes that affect how someone looks (their "phenotype") and how their skin reacts to sun exposure. These features include fair or red hair; pale skin; blue or green eyes, naevi ("moles").

There's lots that can be done to reduce melanoma risk. The most important is to avoid excess sun exposure. High risk families or people who have already had a melanoma should have annual skin checks with their doctor. These checks could include dermoscopy, total-body photography and/or sequential digital dermoscopy imaging.

In some families, the risk is also increased because of a mutation in a particularly gene, such as CDKN2A . This syndrome is sometimes referred to as Familial Atypical Multiple Mole Melanoma syndrome. Other genes that can increase the risk of melanoma included CDK4, BAP1, POT1, ACD, TERF2IP and TERT).

These kind of inherited gene mutations are rare. For example, the average Australian diagnosed with a melanoma has only a 2% chance that it was caused by an inherited CDKN2A mutation. However, for someone who has had 3 or more melanomas and also has 2 or more close family members who have had a melanoma. In countries outside Australia, where sun exposure is much less, the chance may be as high as 60%.

CDKN2A and CDK4 mutations increase melanoma risk and CDKN2A mutations has also been associated with an increased risk of pancreatic and kidney cancer risk, particularly if the individual smokes.

In some families, the melanomas may include melanomas of the eye (uveal melanomas). In this case, a mutation in BAP1 (the BRCA1–associated protein 1) may be considered, particularly if there is also a history of mesothelioma (a cancer of the lining of the chest cavity, usually associated with asbestos exposure). BAP1 related cancer syndrome is very, very rare and scientists are still learning about the lifetime cancer risks.

There is a 50% chance of a person who carries a germline BAP1 or CDKN2A mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early.

For more information, see the links below

  • The US national Institute of health has this technical review of Familial Atypical Multiple Mole Melanoma Syndrome (associated with CDKN2A mutations)
  • The Cancer Institute's eviQ pages provide accurate management and testing guidelines for individuals with inherited cancer syndromes. Currently there are so specific guidelines for hereditary melanoma syndromes. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to and look under Cancer Genetics, Management in the left hand Category Menu
  • These support groups are for individuals and families affected by melanoma: The Melanoma Institute Australia and Melanoma Patients Australia