Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

• Published in: Journal of the American Academy of Dermatology Vol. 74; no. 2; pp. 325 - 332
• Main Authors: Bruno, William, Pastorino, Lorenza, Ghiorzo, Paola, Andreotti, Virginia, Martinuzzi, Claudia, Menin, Chiara, Elefanti, Lisa, Stagni, Camilla, Vecchiato, Antonella, Rodolfo, Monica, Maurichi, Andrea, Manoukian, Siranoush, De Giorgi, Vincenzo, Savarese, Imma, Gensini, Francesca, Borgognoni, Lorenzo, Testori, Alessandro, Spadola, Giuseppe, Mandalà, Mario, Imberti, Gianlorenzo, Savoia, Paola, Astrua, Chiara, Ronco, Anna Maria, Farnetti, Alessandra, Tibiletti, Maria Grazia, Lombardo, Maurizio, Palmieri, Giuseppe, Ayala, Fabrizio, Ascierto, Paolo, Ghigliotti, Giovanni, Muggianu, Marisa, Spagnolo, Francesco, Picasso, Virginia, Tanda, Enrica Teresa, Queirolo, Paola, Bianchi-Scarrà, Giovanna
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2016
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; cyclin-dependent kinase; Cyclin-Dependent Kinase 4 - genetics; cyclin-dependent kinase inhibitor 2A; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Dermatology; family history; genetic assessment; Genetic Counseling; Germ-Line Mutation; Humans; Italy; melanoma; Melanoma - genetics; microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - genetics; Middle Aged; mutation; Mutation Rate; Neoplasms, Multiple Primary - genetics; pancreatic cancer; Patient Selection; Skin Neoplasms - genetics; Young Adult; Italy; SIGU; cyclin-dependent kinase inhibitor 2A; CDKN2A; genetic assessment; melanoma; MITF; CDK; MPM; microphthalmia-associated transcription factor; mutation; SPM; pancreatic cancer; family history; cyclin-dependent kinase; Italian Society of Human Genetics; multiple primary melanoma; single primary melanoma
• ISSN: 0190-9622; 1097-6787; 1097-6787
• DOI: 10.1016/j.jaad.2015.09.053

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.