Background: Multiple primary melanoma (MPM), in concert with a positive family history, is a predictor of cyclin-dependent kinase (CDK) inhibitor 2A (CDKN2A) germline mutations. A rule regarding the presence of either 2 or 3 or more cancer events (melanoma and pancreatic cancer) in low or high melanoma incidence populations, respectively, has been established to select patients for genetic referral.
Objective: We sought to determine the CDKN2A/CDK4/microphthalmia-associated transcription factor mutation rate among Italian patients with MPM to appropriately direct genetic counseling regardless of family history.
Methods: In all, 587 patients with MPM and an equal number with single primary melanomas and control subjects were consecutively enrolled at the participating centers and tested for CDKN2A, CDK4, and microphthalmia-associated transcription factor.
Results: CDKN2A germline mutations were found in 19% of patients with MPM versus 4.4% of patients with single primary melanoma. In familial MPM cases the mutation rate varied from 36.6% to 58.8%, whereas in sporadic MPM cases it varied from 8.2% to 17.6% in patients with 2 and 3 or more melanomas, respectively. The microphthalmia-associated transcription factor E318K mutation accounted for 3% of MPM cases altogether.
Limitations: The study was hospital based, not population based. Rare novel susceptibility genes were not tested.
Conclusion: Italian patients who developed 2 melanomas, even in situ, should be referred for genetic counseling even in the absence of family history.
Keywords: cyclin-dependent kinase; cyclin-dependent kinase inhibitor 2A; family history; genetic assessment; melanoma; microphthalmia-associated transcription factor; mutation; pancreatic cancer.
Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.