Abstract
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 language | English |
|---|---|
| Pages (from-to) | 325-332 |
| Number of pages | 8 |
| Journal | Journal of the American Academy of Dermatology |
| Volume | 74 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2016 |
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Keywords
- 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)
Cite this
Multiple primary melanomas (MPMs) and criteria for genetic assessment : MultiMEL, a multicenter study of the Italian Melanoma Intergroup. / Bruno, William; Pastorino, L.; 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, L.; Testori, Alessandro; Spadola, Giuseppe; Mandalà, M.; Imberti, Gian Lorenzo; Savoia, P.; Astrua, C.; Ronco, Anna M aria; Farnetti, Alessandra; Tibiletti, Maria Grazia; Lombardo, Maurizio; Palmieri, Giuseppe; Ayala, Fabrizio; Ascierto, Paolo Antonio; Ghigliotti, Giovanni; Muggianu, M.; Spagnolo, Francesco; Picasso, Virginia; Tanda, Enrica T eresa; Queirolo, Paola; Bianchi Scarrà, Giovanna.
In: Journal of the American Academy of Dermatology, Vol. 74, No. 2, 01.02.2016, p. 325-332.Research output: Contribution to journal › Article
}
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, L.
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, L.
AU - Testori, Alessandro
AU - Spadola, Giuseppe
AU - Mandalà, M.
AU - Imberti, Gian Lorenzo
AU - Savoia, P.
AU - Astrua, C.
AU - Ronco, Anna M aria
AU - Farnetti, Alessandra
AU - Tibiletti, Maria Grazia
AU - Lombardo, Maurizio
AU - Palmieri, Giuseppe
AU - Ayala, Fabrizio
AU - Ascierto, Paolo Antonio
AU - Ghigliotti, Giovanni
AU - Muggianu, M.
AU - Spagnolo, Francesco
AU - Picasso, Virginia
AU - Tanda, Enrica T eresa
AU - Queirolo, Paola
AU - Bianchi Scarrà, Giovanna
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
UR - http://www.scopus.com/inward/citedby.url?scp=84973407250&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2015.09.053
DO - 10.1016/j.jaad.2015.09.053
M3 - Article
VL - 74
SP - 325
EP - 332
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
SN - 0190-9622
IS - 2
ER -