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

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• 作者：William Bruno ; MD ; PhD^a ; ^c ; Lorenza Pastorino ; PhD^a ; ^c ; ^{l.pastorino@unige.it" class="auth_mail" title="E-mail the corresponding author} ; Paola Ghiorzo ; PhD^a ; ^c ; Virginia Andreotti ; PhD^a ; Claudia Martinuzzi ; MSc^a ; ^b ; Chiara Menin ; PhD^g ; Lisa Elefanti ; PhD^g ; Camilla Stagni ; PhDⁱ ; Antonella Vecchiato ; MD^h ; Monica Rodolfo ; PhD^j ; Andrea Maurichi ; MD^k ; Siranoush Manoukian ; MD ; PhD^l ; Vincenzo De Giorgi ; MD^m ; Imma Savarese ; MD^m ; Francesca Gensini ; MD ; PhDⁿ ; Lorenzo Borgognoni ; MD^o ; Alessandro Testori ; MD^p ; Giuseppe Spadola ; MD^p ; Mario Mandalà ; MD^q ; Gianlorenzo Imberti ; MD^r ; Paola Savoia ; MD^s ; Chiara Astrua ; MD^s ; Anna Maria Ronco ; MD^t ; Alessandra Farnetti ; MD^t ; Maria Grazia Tibiletti ; PhD^u ; Maurizio Lombardo ; MD^v ; Giuseppe Palmieri ; PhD^w ; Fabrizio Ayala ; MD^x ; Paolo Ascierto ; MD^x ; Giovanni Ghigliotti ; MD^d ; Marisa Muggianu ; MD^e ; Francesco Spagnolo ; MD^e ; Virginia Picasso ; MD^f ; Enrica Teresa Tanda ; MD^f ; Paola Queirolo ; MD^f ; Giovanna Bianchi-Scarrà ; PhD^a ; ^c
• 关键词：cyclin-dependent kinase ; cyclin-dependent kinase inhibitor 2A ; family history ; genetic assessment ; melanoma ; microphthalmia-associated transcription factor ; mutation ; pancreatic cancer
• 刊名：Journal of the American Academy of Dermatology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：74
• 期：2
• 页码：325-332
• 全文大小：344 K

文摘

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.