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

William Bruno, Lorenza 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, Lorenzo Borgognoni, Alessandro Testori, Giuseppe Spadola, Mario Mandalà, Gianlorenzo ImbertiPaola Savoia, Chiara Astrua, Anna M aria Ronco, Alessandra Farnetti, Maria G razia Tibiletti, Maurizio Lombardo, Giuseppe Palmieri, Fabrizio Ayala, Paolo Ascierto, Giovanni Ghigliotti, Marisa Muggianu, Francesco Spagnolo, Virginia Picasso, Enrica T eresa Tanda, Paola Queirolo, Giovanna Bianchi-Scarrà

Research output: Contribution to journalArticle

15 Citations (Scopus)

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, Lorenza; 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, Lorenzo; Testori, Alessandro; Spadola, Giuseppe; Mandalà, Mario; Imberti, Gianlorenzo; Savoia, Paola; Astrua, Chiara; Ronco, Anna M aria; Farnetti, Alessandra; Tibiletti, Maria G razia; Lombardo, Maurizio; Palmieri, Giuseppe; Ayala, Fabrizio; Ascierto, Paolo; Ghigliotti, Giovanni; Muggianu, Marisa; 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, G, Savoia, P, Astrua, C, Ronco, AMA, Farnetti, A, Tibiletti, MGR, Lombardo, M, Palmieri, G, Ayala, F, Ascierto, P, 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, Lorenza ; 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, Lorenzo ; Testori, Alessandro ; Spadola, Giuseppe ; Mandalà, Mario ; Imberti, Gianlorenzo ; Savoia, Paola ; Astrua, Chiara ; Ronco, Anna M aria ; Farnetti, Alessandra ; Tibiletti, Maria G razia ; Lombardo, Maurizio ; Palmieri, Giuseppe ; Ayala, Fabrizio ; Ascierto, Paolo ; Ghigliotti, Giovanni ; Muggianu, Marisa ; 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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author = "William Bruno and Lorenza Pastorino and Paola Ghiorzo and Virginia Andreotti and Claudia Martinuzzi and Chiara Menin and Lisa Elefanti and Camilla Stagni and Antonella Vecchiato and Monica Rodolfo and Andrea Maurichi and Siranoush Manoukian and {De Giorgi}, Vincenzo and Imma Savarese and Francesca Gensini and Lorenzo Borgognoni and Alessandro Testori and Giuseppe Spadola and Mario Mandal{\`a} and Gianlorenzo Imberti and Paola Savoia and Chiara Astrua and Ronco, {Anna M aria} and Alessandra Farnetti and Tibiletti, {Maria G razia} and Maurizio Lombardo and Giuseppe Palmieri and Fabrizio Ayala and Paolo Ascierto and Giovanni Ghigliotti and Marisa Muggianu and Francesco Spagnolo and Virginia Picasso and Tanda, {Enrica T eresa} and Paola Queirolo and Giovanna Bianchi-Scarr{\`a}",
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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, 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 M aria

AU - Farnetti, Alessandra

AU - Tibiletti, Maria G razia

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 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.

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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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