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 p16INK4a 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.
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Acknowledgments
This work was supported by grants from FAPESP (2007/04313-2), and the Brazilian National Institute of Science and Technology in Oncogenomics (FAPESP 2008/57887-9, CNPq 573589/08-9). We thank Bianca Lisboa and Gustavo Molina for technical support and the AC Camargo Biobank for processing the DNA samples. We are also grateful to the patients and their families.
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The authors declare that they have no conflict of interest.
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de Ávila, A.L.R., Krepischi, A.C.V., Moredo, L.F. et al. Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma. Familial Cancer 13, 645–649 (2014). https://doi.org/10.1007/s10689-014-9736-1
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DOI: https://doi.org/10.1007/s10689-014-9736-1