CDKN2A Gene Mutation

What is CDKN2A?

CDKN2A is a gene that helps control how cells grow and divide. It does this by making two different proteins:

• p16INK4A (often called p16)
• p14ARF (often called p14)

Some people are born with a change in their CDKN2A gene. These changes are called inherited mutations (or pathogenic variants), and they can increase the risk for certain cancers.

A CDKN2A mutation may affect:

• the p16INK4A protein,
• the p14ARF protein, or
• both proteins.

Most inherited CDKN2A mutations affect the p16INK4A protein.

Which protein is affected can help explain:

• the types of cancer a person may be at higher risk for, and
• which screening and prevention options are recommended.

Which cancers are associated with a CDKN2A mutation?

People with an inherited mutation in CDKN2A have Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome and a high risk for melanoma. Other cancer risks depend on the specific mutation and which proteins are affected. Many CDKN2A mutations are associated with an increased risk for pancreatic cancer. A small number of CDKN2A mutations may also increase the risk for nerve sheath tumors, sarcomas and other types of cancers. 

Does everyone with a CDKN2A mutation develop cancer?

Although the lifetime risk for cancer with a CDKN2A mutation is high, not everyone with a mutation develops cancer. Following the guidelines for screening and prevention increases the chances of preventing cancer or catching it at its earliest and most treatable stage.

What can people with a CDKN2A mutation do?

Experts have created guidelines which estimate cancer risks and outline recommendations for managing these risks in people with a CDKN2A mutation. 

There may be family planning concerns and options for people with an inherited CDKN2A mutation. 

If you test positive for a CDKN2A mutation, you should inform your close blood relatives (first-, second-, and third-degree relatives) about your test results and encourage them to speak with a genetics expert.