title: Early onset may predict G101W CDKN2A founder mutation carrier status in Ligurian melanoma patients.
abstract: Although the presence of multiple cases of melanoma on the same side of a family is the best predictor of germline CDKN2A mutation, other features (i.e. early age at onset) may be useful to identify carriers. We analysed the records of 682 hospital-based Ligurian melanoma patients. Of these, 238 cases (34 familial, 14 non-familial multiple primary and 190 non-familial single primary melanomas) were consecutively enrolled for screening of the CDKN2A and CDK4 genes. Screening of the 34 familial patients revealed that nine were carriers of the CDKN2A G101W founder mutation. Of the 14 non-familial multiple primary melanoma patients, three carried the G101W founder mutation and one the P48T mutation. For the non-familial patients with a single melanoma, 17 of 190 carried germline CDKN2A mutations, with most (16/17) carrying the G101W Ligurian founder mutation and one a novel single base pair substitution, D74Y. The effect of mutation on age at diagnosis was significant (P=0.012) after correcting for melanoma type (familial or non-familial), number of primaries (single or multiple), gender and disease occurrence (incident or prevalent). Early age at onset may be a good predictor of CDKN2A mutation in Liguria, where the G101W founder mutation is prevalent among melanoma patients, independent of family history.
authors.affiliation: Dipartimento di Oncologia, Biologia e Genetica, Universita' di Genova, V. le Benedetto XV, 6, 16132 Genova, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Mantelli
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiorzo
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.forename: William
authors.initials: W
authors.lastname: Bruno
authors.forename: Sara
authors.initials: S
authors.lastname: Gargiulo
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Sara
authors.initials: S
authors.lastname: Gliori
authors.forename: Stefania
authors.initials: S
authors.lastname: Vecchio
authors.forename: Paola
authors.initials: P
authors.lastname: Ciotti
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Sertoli
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
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; D017668:Age of Onset; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008499:Medical Records; D008545:Melanoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm