What Is a CDKN2A Mutation? How High Are Melanoma and Pancreatic Cancer Risks?

What is an inherited CDKN2A mutation? General information for carriers

• The name CDKN2A comes from "Cyclin-Dependent Kinase Inhibitor 2A". The CDKN2A gene is located on chromosome 9 and provides instructions for making several tumor suppressor proteins.
• The CDKN2A gene makes more than one protein, and inherited mutations in the gene are named after the protein affected by the mutation.
• Mutations in CDKN2A (p16INK4a) and a syndrome called Familial Atypical Mole / Multiple Melanoma (FAMMM) + Pancreatic Cancer are associated.
• With mutations in CDKN2A (p14ARF), the risk of melanoma may increase.
• People carrying an inherited CDKN2A mutation have an increased risk of certain cancers.
• There are guidelines for cancer screening and prevention in people carrying a CDKN2A mutation.
• People carrying an inherited CDKN2A mutation may participate in appropriate clinical trials. For people carrying a CDKN2A mutation who have been diagnosed with cancer, certain treatments or clinical trials may be available.

Which cancer risks does an inherited CDKN2A mutation increase?

If you test positive for an inherited CDKN2A mutation, a team that can review your and your family's cancer history and help you choose the best plan for managing your cancer risk — specifically, a multidisciplinary oncology team — is recommended as a point of contact.

• People with a CDKN2A mutation have a lifetime risk of 28 – 67% of developing melanoma. The lifetime risk of melanoma for someone who cannot carry a mutation is approximately 2.5%. People carrying a CDKN2A mutation:
  • Often develop melanoma at a young age (before age 50).
  • May develop two or more melanomas during their lifetime.

• People carrying a CDKN2A mutation have a lifetime risk of up to 17% that pancreatic cancer may develop.
• The risks may be higher for people with a close relative diagnosed with melanoma or pancreatic cancer.
• Some studies suggest that smoking may increase cancer risks in people carrying a CDKN2A mutation.

How should risk be managed for people carrying an inherited CDKN2A mutation?

The following are risk management guidelines for people with a CDKN2A mutation. It is recommended that you consult a multidisciplinary oncology team that can review your and your family's cancer history and help you decide on the best risk management plan.

Melanoma screening and prevention

• Examine yourself monthly to notice skin changes. Ask a friend or family member to help with areas of your body that you cannot see.
• Keep monitoring for any changes in the shape, size, and color of your moles.
• Dermatologists may take pictures of your skin or moles, known as mole mapping, or take photographs of your whole body. They may also examine your moles with a portable device called a dermatoscope. The doctor removes any suspicious mole or other skin change so that the tissue can be analyzed under a microscope.
• Because of the high risk of multiple melanomas, people with familial melanoma and / or CDN2A gene mutations should protect themselves from the sun and take protective measures outdoors. They should avoid going outside during peak sun exposure hours (between 10.00 and 16.00), stay in the shade as much as possible when outdoors, apply sunscreen frequently and generously, wear a hat with a brim at least 7 – 8 cm wide that goes all the way around the head, and wear protective clothing covering the arms and legs.
• Children with a family history of familial melanoma and / or CDKN2A gene mutations should begin screening by age 10.
• In people with melanoma, a dermatologist should examine the entire skin every 3 or 6 months, depending on the number of moles, the time since diagnosis, the skin type, and the type of melanoma.

Pancreatic cancer screening or prevention

• Consider pancreatic cancer screening in the early 40s with one or both of the following:
  • Contrast-enhanced MRI-MRCP (magnetic resonance cholangiopancreatography)
  • EUS (endoscopic ultrasound)

• Before undergoing screening, people can talk to their doctors about the potential benefits, risks, cost, and limitations of screening.
• US-NCCN (United States National Comprehensive Cancer Network) recommends screening at an experienced facility, ideally in a research setting.

Cancer treatment for people carrying an inherited CDKN2A mutation

There is currently neither an approved cancer treatment specifically for people carrying a CDKN2A mutation nor a cancer treatment guideline written specifically for them. To help experts learn which treatments will work best for someone carrying an inherited CDKN2A mutation, participation in a clinical trial is worth considering.

Other medical concerns for people carrying an inherited CDNK2A mutation

People carrying an inherited CDNK2A mutation have a 50% chance of passing the mutation to each of their children. For parents seeking to select embryos without inherited CDKN2A mutations, assisted reproductive technology and preimplantation genetic diagnosis are available options.