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

William Bruno, L. Pastorino, Paola Ghiorzo, Virginia Andreotti, Claudia Martinuzzi, Chiara Menin, Lisa Elefanti, Camilla Stagni, Antonella Vecchiato, Monica Rodolfo, Andrea Maurichi, Siranoush Manoukian, Vincenzo De Giorgi, Imma Savarese, Francesca Gensini, L. Borgognoni, Alessandro Testori, Giuseppe Spadola, M. Mandalà, Gian Lorenzo ImbertiP. Savoia, C. Astrua, Anna M aria Ronco, Alessandra Farnetti, Maria Grazia Tibiletti, Maurizio Lombardo, Giuseppe Palmieri, Fabrizio Ayala, Paolo Antonio Ascierto, Giovanni Ghigliotti, M. Muggianu, Francesco Spagnolo, Virginia Picasso, Enrica T eresa Tanda, Paola Queirolo, Giovanna Bianchi Scarrà

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)325-332
Number of pages8
JournalJournal of the American Academy of Dermatology
Issue number2
Publication statusPublished - Feb 1 2016


  • cyclin-dependent kinase
  • cyclin-dependent kinase inhibitor 2A
  • family history
  • genetic assessment
  • melanoma
  • microphthalmia-associated transcription factor
  • mutation
  • pancreatic cancer

ASJC Scopus subject areas

  • Medicine(all)


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