title: Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma.
abstract: Approximately 10 % of all cutaneous melanoma cases occur in a familial context. The major susceptibility gene for familial melanoma is CDKN2A. In Latin America, genetic studies investigating melanoma predisposition are scarce. The aim of this work was to investigate germline CDKN2A point mutations and genomic rearrangements in a cohort of 59 Brazilian melanoma-prone patients. Screening of CDKN2A alterations was performed by sequencing and multiplex ligation probe amplification. Germline CDKN2A mutations affecting p16(INK4a) were detected in 8 unrelated probands (13.6 %), including 7 familial cases and one patient with multiple melanomas; 4 out of 8 mutation carriers met the criteria for familial melanoma and had multiple primary lesions. Although this study adds to the literature on melanoma susceptibility in Latin America, it is limited by the small size of the cohort. Our findings suggest that stringent inclusion criteria led to a substantially increased rate of CDKN2A mutation detection. This consideration should be taken into account when referring patients for genetic screening in a setting of limited budget, such as in developing countries.
authors.affiliation: Department of Skin Cancer, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Alexandre Leon Ribeiro
authors.initials: AL
authors.lastname: de Ávila
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
authors.forename: Luciana Facure
authors.initials: LF
authors.lastname: Moredo
authors.forename: Talita Ferreira Marques
authors.initials: TF
authors.lastname: Aguiar
authors.forename: Felipe Carneiro
authors.initials: FC
authors.lastname: da Silva
authors.forename: Bianca Costa Soares
authors.initials: BC
authors.lastname: de Sá
authors.forename: Amanda França
authors.initials: AF
authors.lastname: de Nóbrega
authors.forename: Maria Isabel Waddington
authors.initials: MI
authors.lastname: Achatz
authors.forename: João Pedreira
authors.initials: JP
authors.lastname: Duprat
authors.forename: Gilles
authors.initials: G
authors.lastname: Landman
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
mesh_terms: D000328:Adult; D001938:Brazil; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D012878:Skin Neoplasms; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16