title: Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup.
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.
  
  
  CONCLUSIONS
  The study was hospital based, not population based. Rare novel susceptibility genes were not tested.
  
  
  CONCLUSIONS
  Italian patients who developed 2 melanomas, even in situ, should be referred for genetic counseling even in the absence of family history.
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: William
authors.initials: W
authors.lastname: Bruno
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. Electronic address: l.pastorino@unige.it.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Andreotti
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martinuzzi
authors.affiliation: Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, Istituto Oncologico Veneto (IOV)-IRCCS, Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Menin
authors.affiliation: Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, Istituto Oncologico Veneto (IOV)-IRCCS, Padua, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Elefanti
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stagni
authors.affiliation: Melanoma and Soft Tissue Sarcoma Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Vecchiato
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
authors.affiliation: Melanoma and Sarcoma Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maurichi
authors.affiliation: Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.affiliation: Department of Dermatology, University of Florence, Florence, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Giorgi
authors.affiliation: Department of Dermatology, University of Florence, Florence, Italy.
authors.forename: Imma
authors.initials: I
authors.lastname: Savarese
authors.affiliation: Unit of Medical Genetics, Department of Biomedical Experimental and Clinical Sciences, University of Florence, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gensini
authors.affiliation: Plastic Surgery Unit, Regional Melanoma Referral Center, Santa Maria Annunziata Hospital, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Borgognoni
authors.affiliation: Division of Dermatoncological Surgery, European Institute of Oncology, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.affiliation: Division of Dermatoncological Surgery, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spadola
authors.affiliation: Medical Oncology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Mandalà
authors.affiliation: Dermatology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Gianlorenzo
authors.initials: G
authors.lastname: Imberti
authors.affiliation: Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Savoia
authors.affiliation: Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Astrua
authors.affiliation: Dermatoncological Surgery Unit, Presidio Sanitario Gradenigo, Turin, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ronco
authors.affiliation: Dermatoncological Surgery Unit, Presidio Sanitario Gradenigo, Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Farnetti
authors.affiliation: Anatomopathology Unit, Università dell'Insubria, Ospedale di Circolo, Varese, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tibiletti
authors.affiliation: Dermatology Unit, Ospedale di Circolo, Varese, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Lombardo
authors.affiliation: Cancer Genetics Unit, Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Department of Melanoma, National Cancer Institute Pascale Foundation, Naples, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ayala
authors.affiliation: Department of Melanoma, National Cancer Institute Pascale Foundation, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascierto
authors.affiliation: Dermatology Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ghigliotti
authors.affiliation: Department of Plastic and Reconstructive Surgery, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Muggianu
authors.affiliation: Department of Plastic and Reconstructive Surgery, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spagnolo
authors.affiliation: Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale dei Tumori (IST) Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Picasso
authors.affiliation: Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale dei Tumori (IST) Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Enrica Teresa
authors.initials: ET
authors.lastname: Tanda
authors.affiliation: Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-Istituto Nazionale dei Tumori (IST) Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.affiliation: Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy; Genetics of Rare Cancers, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarrà
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005817:Genetic Counseling; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008545:Melanoma / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D008875:Middle Aged; D059645:Mutation Rate; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D018579:Patient Selection; D012878:Skin Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D051739:Microphthalmia-Associated Transcription Factor; D051358:Cyclin-Dependent Kinase 4
keywords: cyclin-dependent kinase; cyclin-dependent kinase inhibitor 2A; family history; genetic assessment; melanoma; microphthalmia-associated transcription factor; mutation; pancreatic cancer