William Bruno1, Lorenza Pastorino2, Paola Ghiorzo1, Virginia Andreotti3, Claudia Martinuzzi4, Chiara Menin5, Lisa Elefanti5, Camilla Stagni6, Antonella Vecchiato7, Monica Rodolfo8, Andrea Maurichi9, Siranoush Manoukian10, Vincenzo De Giorgi11, Imma Savarese11, Francesca Gensini12, Lorenzo Borgognoni13, Alessandro Testori14, Giuseppe Spadola14, Mario Mandalà15, Gianlorenzo Imberti16, Paola Savoia17, Chiara Astrua17, Anna Maria Ronco18, Alessandra Farnetti18, Maria Grazia Tibiletti19, Maurizio Lombardo20, Giuseppe Palmieri21, Fabrizio Ayala22, Paolo Ascierto22, Giovanni Ghigliotti23, Marisa Muggianu24, Francesco Spagnolo24, Virginia Picasso25, Enrica Teresa Tanda25, Paola Queirolo25, Giovanna Bianchi-Scarrà1. 1. 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. 2. 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. 3. Department of Internal Medicine, Medical Specialties and Surgical Science and Integrated Diagnostics, University of Genoa, Genoa, Italy. 4. 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. 5. Immunology and Molecular Oncology Unit, Veneto Institute of Oncology, Istituto Oncologico Veneto (IOV)-IRCCS, Padua, Italy. 6. Section of Oncology and Immunology, Department of Surgery, Oncology, and Gastroenterology, University of Padua, Padua, Italy. 7. Melanoma and Soft Tissue Sarcoma Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy. 8. Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 9. Melanoma and Sarcoma Surgery Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 10. Medical Genetics Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 11. Department of Dermatology, University of Florence, Florence, Italy. 12. Unit of Medical Genetics, Department of Biomedical Experimental and Clinical Sciences, University of Florence, Florence, Italy. 13. Plastic Surgery Unit, Regional Melanoma Referral Center, Santa Maria Annunziata Hospital, Florence, Italy. 14. Division of Dermatoncological Surgery, European Institute of Oncology, Milan, Italy. 15. Medical Oncology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 16. Dermatology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy. 17. Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy. 18. Dermatoncological Surgery Unit, Presidio Sanitario Gradenigo, Turin, Italy. 19. Anatomopathology Unit, Università dell'Insubria, Ospedale di Circolo, Varese, Italy. 20. Dermatology Unit, Ospedale di Circolo, Varese, Italy. 21. Cancer Genetics Unit, Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy. 22. Department of Melanoma, National Cancer Institute Pascale Foundation, Naples, Italy. 23. Dermatology Unit, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 24. Department of Plastic and Reconstructive Surgery, IRCCS AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. 25. 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.
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.
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.
Authors: Christopher Li; Tong Liu; Bin Liu; Rolando Hernandez; Julio C Facelli; Douglas Grossman Journal: Pigment Cell Melanoma Res Date: 2019-05-03 Impact factor: 4.693
Authors: Adi Nosrati; Wesley Y Yu; Joseph McGuire; Ann Griffin; Juliana Rocha de Souza; Rasnik Singh; Eleni Linos; Mary Margaret Chren; Barbara Grimes; Nicholas P Jewell; Maria L Wei Journal: J Invest Dermatol Date: 2018-07-19 Impact factor: 7.590