title: High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families.
abstract: CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.
authors.affiliation: Dipartimento di Oncologia, Biologia e Genetica, Università degli Studi di Genova, Genova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Mantelli
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.forename: Paola
authors.initials: P
authors.lastname: Ciotti
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Lantieri
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Caterina
authors.initials: C
authors.lastname: Catricalà
authors.forename: Gabriella Della
authors.initials: GD
authors.lastname: Torre
authors.forename: Ugo
authors.initials: U
authors.lastname: Folco
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
authors.forename: Laura
authors.initials: L
authors.lastname: Padovani
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.forename: Dario
authors.initials: D
authors.lastname: Rovini
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Rainero
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Santi
authors.forename: Roberto M
authors.initials: RM
authors.lastname: Sertoli
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi-Scarrà
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm