CDKN2A Cancer Predisposition

Excerpt

Clinical characteristics: CDKN2A cancer predisposition is characterized by an increased risk of developing multiple cutaneous melanomas, pancreatic cancer, and other tumors including gliomas and astrocytomas. Some affected individuals have a high total nevus count (often >50 nevi) and atypical-appearing nevi, although the number and extent of atypical nevi can vary significantly.

Diagnosis/testing: The diagnosis of CDKN2A cancer predisposition is established in a proband by identification of a heterozygous germline pathogenic variant in CDKN2A by molecular genetic testing.

Management: Treatment of manifestations: Standard treatment for melanoma, pancreatic cancer, and other cancers.

Surveillance: Dermatologic examination for melanoma every six months; monthly self-skin examinations; annual alternating magnetic resonance cholangiopancreatography and endoscopic ultrasound starting at age 40 years or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier; full-body and brain MRI in those with a CDKN2A pathogenic variant affecting the p14^ARF isoform in the setting of a family history of nervous system tumors.

Agents/circumstances to avoid: Ultraviolet light exposure, particularly sunburns and tanning booths; tobacco use.

Evaluation of relatives at risk: Molecular genetic testing for the familial CDKN2A pathogenic variant is recommended for at-risk relatives of an affected individual. Family members who have a CDKN2A pathogenic variant should be offered regular lifelong surveillance. At-risk family members whose genetic status is unknown should undergo skin exams at their well child / health maintenance visits.

Genetic counseling: CDKN2A cancer predisposition is inherited in an autosomal dominant manner. The majority of individuals diagnosed with CDKN2A cancer predisposition inherited the CDKN2A germline pathogenic variant from a parent. A parent with a CDKN2A pathogenic variant may or may not have had a cancer diagnosis. Each child of an individual with CDKN2A cancer predisposition has a 50% chance of inheriting the pathogenic variant. Once the CDKN2A pathogenic variant has been identified in an affected family member, predictive testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.