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 Imberti & 16 others P. 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 journalArticle

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 languageEnglish
Pages (from-to)325-332
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume74
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Multicenter Studies
Melanoma
Microphthalmia-Associated Transcription Factor
Germ-Line Mutation
Genetic Counseling
Mutation Rate
Cyclin-Dependent Kinase Inhibitor p16
Pancreatic Neoplasms
Population
Referral and Consultation
Mutation

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 journalArticle

Bruno, W, Pastorino, L, Ghiorzo, P, Andreotti, V, Martinuzzi, C, Menin, C, Elefanti, L, Stagni, C, Vecchiato, A, Rodolfo, M, Maurichi, A, Manoukian, S, De Giorgi, V, Savarese, I, Gensini, F, Borgognoni, L, Testori, A, Spadola, G, Mandalà, M, Imberti, GL, Savoia, P, Astrua, C, Ronco, AMA, Farnetti, A, Tibiletti, MG, Lombardo, M, Palmieri, G, Ayala, F, Ascierto, PA, Ghigliotti, G, Muggianu, M, Spagnolo, F, Picasso, V, Tanda, ETE, Queirolo, P & Bianchi Scarrà, G 2016, 'Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup', Journal of the American Academy of Dermatology, vol. 74, no. 2, pp. 325-332. https://doi.org/10.1016/j.jaad.2015.09.053
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. / Multiple primary melanomas (MPMs) and criteria for genetic assessment : MultiMEL, a multicenter study of the Italian Melanoma Intergroup. In: Journal of the American Academy of Dermatology. 2016 ; Vol. 74, No. 2. pp. 325-332.
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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.",
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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

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U2 - 10.1016/j.jaad.2015.09.053

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