Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy.
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.
Casula
Milena
M
Istituto di Chimica Biomolecolare-Consiglio Nazionale Ricerche, Traversa La Crucca, 3 - Reg. Baldinca, 07040 Li Punti-Sassari (SS), Italy.
Colombino
Maria
M
Satta
Maria P
MP
Cossu
Antonio
A
Lissia
Amelia
A
Budroni
Mario
M
Simeone
Ester
E
Calemma
Rosa
R
Loddo
Cinzia
C
Caracò
Corrado
C
Mozzillo
Nicola
N
Daponte
Antonio
A
Comella
Giuseppe
G
Canzanella
Sergio
S
Guida
Michele
M
Castello
Giuseppe
G
Ascierto
Paolo A
PA
Palmieri
Giuseppe
G
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*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf