TY - JOUR
T1 - Multiple primary melanomas (MPMs) and criteria for genetic assessment
T2 - MultiMEL, a multicenter study of the Italian Melanoma Intergroup
AU - Bruno, William
AU - Pastorino, Lorenza
AU - Ghiorzo, Paola
AU - Andreotti, Virginia
AU - Martinuzzi, Claudia
AU - Menin, Chiara
AU - Elefanti, Lisa
AU - Stagni, Camilla
AU - Vecchiato, Antonella
AU - Rodolfo, Monica
AU - Maurichi, Andrea
AU - Manoukian, Siranoush
AU - De Giorgi, Vincenzo
AU - Savarese, Imma
AU - Gensini, Francesca
AU - Borgognoni, Lorenzo
AU - Testori, Alessandro
AU - Spadola, Giuseppe
AU - Mandalà, Mario
AU - Imberti, Gianlorenzo
AU - Savoia, Paola
AU - Astrua, Chiara
AU - Ronco, Anna Maria
AU - Farnetti, Alessandra
AU - Tibiletti, Maria Grazia
AU - Lombardo, Maurizio
AU - Palmieri, Giuseppe
AU - Ayala, Fabrizio
AU - Ascierto, Paolo
AU - Ghigliotti, Giovanni
AU - Muggianu, Marisa
AU - Spagnolo, Francesco
AU - Picasso, Virginia
AU - Tanda, Enrica Teresa
AU - Queirolo, Paola
AU - Bianchi-Scarrà, Giovanna
N1 - Publisher Copyright:
© 2015 American Academy of Dermatology, Inc.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - cyclin-dependent kinase
KW - cyclin-dependent kinase inhibitor 2A
KW - family history
KW - genetic assessment
KW - melanoma
KW - microphthalmia-associated transcription factor
KW - mutation
KW - pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=84973407250&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2015.09.053
DO - 10.1016/j.jaad.2015.09.053
M3 - Article
SN - 0190-9622
VL - 74
SP - 325
EP - 332
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 2
ER -