title: Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy.
abstract: Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR)=6.31; p=0.0009), multiple primary melanomas (RR=3.43; p=0.0014), and early onset age (RR=4.56; p=0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.
authors.affiliation: Istituto di Chimica Biomolecolare-Consiglio Nazionale Ricerche, Traversa La Crucca, 3 - Reg. Baldinca, 07040 Li Punti-Sassari (SS), Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Casula
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Maria P
authors.initials: MP
authors.lastname: Satta
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Amelia
authors.initials: A
authors.lastname: Lissia
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.forename: Rosa
authors.initials: R
authors.lastname: Calemma
authors.forename: Cinzia
authors.initials: C
authors.lastname: Loddo
authors.forename: Corrado
authors.initials: C
authors.lastname: Caracò
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Daponte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Comella
authors.forename: Sergio
authors.initials: S
authors.lastname: Canzanella
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D024522:Genes, BRCA2; D019942:Genes, p16; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012044:Regression Analysis; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf