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.
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.
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.
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.
The study was hospital based, not population based. Rare novel susceptibility genes were not tested.
Italian patients who developed 2 melanomas, even in situ, should be referred for genetic counseling even in the absence of family history.Le texte complet de cet article est disponible en PDF.
Key words : cyclin-dependent kinase, cyclin-dependent kinase inhibitor 2A, family history, genetic assessment, melanoma, microphthalmia-associated transcription factor, mutation, pancreatic cancer
Abbreviations used : CDK, CDKN2A, MITF, MPM, SIGU, SPM
| Drs Queirolo and Bianchi-Scarrà contributed equally to this study.
| Partially funded by Associazione Italiana per la Ricerca sul Cancro (AIRC) 15460 to Dr Ghiorzo, University of Genoa Progetto Ricerca Ateneo (PRA) 2013-2014 to Dr Ghiorzo, Italian Ministry of Health funds to Drs Bianchi-Scarrà and Ghiorzo, Italian Melanoma Intergroup fellowship to Dr Andreotti, Italian Melanoma Intergroup and Emme Rouge Onlus funds in memory of Mara Nahum to Drs Bruno and Rodolfo, and Sardinia Regional Government (Regione Autonoma della Sardegna) funds to Dr Palmieri.
| Conflicts of interest: None declared.