Clinical testing is available to identify germline mutations in CDKN2A. Multiple centers in the United States and overseas offer sequence analysis of the entire coding region, and a number of centers perform deletion and duplication analysis. For information on genetic testing laboratories, see GeneTests: Laboratory Directory.
Expert opinion regarding testing for germline mutations of CDKN2A follows two divergent schools of thought. Arguments for genetic testing include the value of identifying a cause of disease for the individual tested, the possibility of improved compliance with prevention protocols in individuals with an identified mutation, and the reassurance of a negative testing result in individuals in a mutation-carrying family. However, a negative test result in a family that does not have a known mutation is uninformative; the genetic cause of disease in these patients must still be identified. It should also be noted that members of CDKN2A mutation-carrying families who do not carry the mutation themselves remain at increased risk of melanoma. At this time, identification of a CDKN2A mutation does not affect the clinical management of the affected patient or family members. Close dermatologic follow-up of these people is indicated, regardless of genetic testing result, and pancreatic cancer screening has unclear utility, as discussed below.
If genetic testing is undertaken in this population, experts suggest that it be performed after complete genetic counseling by a qualified genetics professional who is knowledgeable about the condition.
For information on psychosocial issues related to genetic testing for melanoma risk, refer to the section on Psychosocial Issues in Familial Melanoma.
Management of members of melanoma-prone families
High-risk individuals, including first-degree family members in melanoma-prone families should be educated about sun safety and warning signs of melanoma. Regular examination of the skin by a health care provider experienced in the evaluation of pigmented lesions is also recommended. One guideline suggests initiation of examination at age 10 years and conducting exams on a semiannual basis until nevi are considered stable, followed by annual examinations. These individuals should also be taught skin self-examination techniques, to be performed on a monthly basis. Observation of lesions may be aided by techniques such as full-body photography and dermoscopy. A cost-utility analysis has demonstrated the benefits of screening in the high-risk population.
Biopsies of skin lesions in the high-risk population should be performed using the same criteria as those used for lesions in the general population. Prophylactic removal of nevi without clinically worrisome characteristics is not recommended. The reasons for this are practical: many individuals in these families have a large number of nevi, and complete removal of them all is not feasible, since new atypical nevi continue to develop. In addition, individuals with increased susceptibility to melanoma may have cancer arise de novo, without a precursor lesion such as a nevus.