PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.
PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.
Authors: Giuseppe Palmieri; Maria Colombino; Milena Casula; Mario Budroni; Antonella Manca; Maria Cristina Sini; Amelia Lissia; Ignazio Stanganelli; Paolo A Ascierto; Antonio Cossu Journal: Melanoma Manag Date: 2015-05-18
Authors: Miriam Potrony; Celia Badenas; Paula Aguilera; Joan Anton Puig-Butille; Cristina Carrera; Josep Malvehy; Susana Puig Journal: Ann Transl Med Date: 2015-09
Authors: M Potrony; J A Puig-Butille; M Ribera-Sola; V Iyer; C D Robles-Espinoza; P Aguilera; C Carrera; J Malvehy; C Badenas; M T Landi; D J Adams; S Puig Journal: Br J Dermatol Date: 2019-02-27 Impact factor: 9.302
Authors: P Aguilera; C Carrera; J A Puig-Butille; C Badenas; M Lecha; S González; J Malvehy; S Puig Journal: J Eur Acad Dermatol Venereol Date: 2012-07-31 Impact factor: 6.166
Authors: F Demenais; H Mohamdi; V Chaudru; A M Goldstein; J A Newton Bishop; D T Bishop; P A Kanetsky; N K Hayward; E Gillanders; D E Elder; M F Avril; E Azizi; P van Belle; W Bergman; G Bianchi-Scarrà; B Bressac-de Paillerets; D Calista; C Carrera; J Hansson; M Harland; D Hogg; V Höiom; E A Holland; C Ingvar; M T Landi; J M Lang; R M Mackie; G J Mann; M E Ming; C J Njauw; H Olsson; J Palmer; L Pastorino; S Puig; J Randerson-Moor; M Stark; H Tsao; M A Tucker; P van der Velden; X R Yang; N Gruis Journal: J Natl Cancer Inst Date: 2010-09-28 Impact factor: 13.506
Authors: Giuseppe Palmieri; Mariaelena Capone; Maria Libera Ascierto; Giusy Gentilcore; David F Stroncek; Milena Casula; Maria Cristina Sini; Marco Palla; Nicola Mozzillo; Paolo A Ascierto Journal: J Transl Med Date: 2009-10-14 Impact factor: 5.531