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

卷:74

Article

Bruno, William^1,3  Pastorino, Lorenza^1,3  Ghiorzo, Paola^1,3  Andreotti, Virginia¹  Martinuzzi, Claudia^1,2  Menin, Chiara⁷  Elefanti, Lisa⁷  Stagni, Camilla⁹  Vecchiato, Antonella⁸  Rodolfo, Monica¹⁰  Maurichi, Andrea¹¹  Manoukian, Siranoush¹²  De Giorgi, Vincenzo¹³  Savarese, Imma¹³  Gensini, Francesca¹⁴  Borgognoni, Lorenzo¹⁵  Testori, Alessandro¹⁶  Spadola, Giuseppe¹⁶  Mandala, Mario¹⁷  Imberti, Gianlorenzo¹⁸  Savoia, Paola¹⁹  Astrua, Chiara¹⁹  Ronco, Anna Maria²⁰  Farnetti, Alessandra²⁰  Tibiletti, Maria Grazia²¹  Lombardo, Maurizio²²  Palmieri, Giuseppe²³  Ayala, Fabrizio²⁴  Ascierto, Paolo²⁴  Ghigliotti, Giovanni⁴  Muggianu, Marisa⁵  Spagnolo, Francesco⁵  Picasso, Virginia⁶  Tanda, Enrica Teresa⁶  Queirolo, Paola⁶  Bianchi-Scarra, Giovanna^1,3 

[1] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy

[2] Univ Genoa, Dept Med Specialties & Surg Sci & Integrated Diag, I-16132 Genoa, Italy

[3] Azienda Osped Univ AOU San Martino, Ist Nazl Tumori, Ist Nazl Ric Canc, IRCCS,Genet Rare Canc, Genoa, Italy

[4] Azienda Osped Univ AOU San Martino, Ist Nazl Tumori, Ist Nazl Ric Canc, IRCCS,Dermatol Unit, Genoa, Italy

[5] Azienda Osped Univ AOU San Martino, Ist Nazl Tumori, Ist Nazl Ric Canc, IRCCS,Dept Plast & Reconstruct Surg, Genoa, Italy

[6] Azienda Osped Univ AOU San Martino, Ist Nazl Tumori, Ist Nazl Ric Canc, IRCCS,Dept Med Oncol, Genoa, Italy

[7] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy

[8] IRCCS, IOV, Melanoma & Soft Tissue Sarcoma Unit, Padua, Italy

[9] Univ Padua, Dept Surg Oncol & Gastroenterol, Sect Oncol & Immunol, I-35100 Padua, Italy

[10] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol, Milan, Italy

[11] Fdn IRCCS Ist Nazl Tumori, Melanoma & Sarcoma Surg Unit, Milan, Italy

[12] Fdn IRCCS Ist Nazl Tumori, Med Genet Unit, Milan, Italy

[13] Univ Florence, Dept Dermatol, I-50121 Florence, Italy

[14] Univ Florence, Unit Med Genet, Dept Biomed Expt & Clin Sci, I-50121 Florence, Italy

[15] Santa Maria Annunziata Hosp, Reg Melanoma Referral Ctr, Plast Surg Unit, Florence, Italy

[16] European Inst Oncol, Div Dermatoncol Surg, Milan, Italy

[17] Osped Papa Giovanni XXIII, Med Oncol Unit, Bergamo, Italy

[18] Osped Papa Giovanni XXIII, Dermatol Unit, Bergamo, Italy

[19] Univ Turin, Dermatol Sect, Dept Med Sci, I-10124 Turin, Italy

[20] Presidio Sanit Gradenigo, Dermatoncol Surg Unit, Turin, Italy

[21] Univ Insubria, Anatomopathol Unit, Gothenburg, Sweden

[22] Osped Circolo Varese, Dermatol Unit, Varese, Italy

[23] CNR, Inst Biomol Chem, Canc Genet Unit, Sassari, Italy

[24] Pascale Fdn, Natl Canc Inst, Dept Melanoma, Naples, Italy

关键词: cyclin-dependent kinase;    cyclin-dependent kinase inhibitor 2A;    family history;    genetic assessment;    melanoma;    microphthalmia-associated transcription factor;    mutation;    pancreatic cancer;   

DOI  :  10.1016/j.jaad.2015.09.053

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free