Malignant Melanoma and the CDKN2A gene

Malignant Melanoma and the CDKN2A gene

In Australia, melanoma is the 3rd most common cancer. It affects 1 in18 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 and naevi ("moles"). What colour your skin is and how it reacts to UV radiation is determined by multiple different genes interacting together. Genetic testing is not normally performed in this situation and standard sun sense guidelines should be followed.

There's lots that can be done to reduce melanoma risk. The most important is to avoid excess sun exposure. Families at increased risk, or people who have already had a melanoma, should have annual skin checks with their doctor.

In some families, the risk is also increased because of a mutation in a particular 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.

A CDKN2A mutation may be present if you have had multiple melanoma, especially if they have occurred at a young age, or if you have multiple close relatives with melanoma, Genetic testing in this case may help to determine risk and guide screening.

Because the lifetime melanoma risk may be more than 50%, screening starts at age 18 and includes dermoscopy, total-body photography and/or sequential digital dermoscopy imaging, performed every 6 months.

An individual with a CDKN2A mutation is at increased risk of pancreatic and kidney cancer risk, particularly if they smoke.

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, pronounced Bap One) 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 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.

Does this sound like you or your family?
Have you had multiple melanomas at a young age or has a CDKN2A mutation been detected in a blood relative?
Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.

These links may be useful

  • These support groups are for individuals and families affected by melanoma: The Melanoma Institute Australia and Melanoma Patients Australia
  • The Cancer Genetics section of the Cancer Institute's eviQ website provides up-to-date Australian-based management guidelines as well as the lifetime risk of tumours and cancers for individuals with CDKN2A and BAP1 mutations.