Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma

• Published in: Familial cancer 2014-12, Vol.13 (4), p.645-649
• Main Authors: de Ávila, Alexandre Leon Ribeiro, Krepischi, Ana Cristina Victorino, Moredo, Luciana Facure, Aguiar, Talita Ferreira Marques, da Silva, Felipe Carneiro, de Sá, Bianca Costa Soares, de Nóbrega, Amanda França, Achatz, Maria Isabel Waddington, Duprat, João Pedreira, Landman, Gilles, Carraro, Dirce Maria
• Format: Article
• Language: English
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; Brazil; Cancer Research; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Epidemiology; Female; Genes, p16; Genetic Predisposition to Disease - genetics; Germ-Line Mutation; Human Genetics; Humans; Male; Melanoma - genetics; Melanoma, Cutaneous Malignant; Middle Aged; Multiplex Polymerase Chain Reaction; Short Communication; Skin Neoplasms; Young Adult
• ISSN: 1389-9600; 1573-7292
• DOI: 10.1007/s10689-014-9736-1

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.