| Autor: |
Soares de Sá BC; Skin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, Brazil., Moredo LF; Skin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, Brazil., Torrezan GT; Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, 440 Taguá St., São Paulo 01508-010, Brazil., Fidalgo F; Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, Brazil., de Araújo ÉSS; Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, Brazil., Formiga MN; Oncogenetics Department, A.C. Camargo Cancer Center, São Paulo 01509-900, Brazil., Duprat JP; Skin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, Brazil., Carraro DM; Clinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, 440 Taguá St., São Paulo 01508-010, Brazil. |
| Abstrakt: |
Increased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as CDKN2A and CDK4 , risk variants in low- to moderate-penetrance genes ( MC1R and MITF ), and possibly due to variants in emerging genes, such as ACD , TERF2IP, and TERT . We aimed to identify germline variants in high- and low- to moderate-penetrance melanoma risk genes in Brazilian patients with clinical criteria for familial melanoma syndrome. We selected patients with three or more melanomas or melanoma patients from families with three tumors (melanoma and pancreatic cancer) in first- or second-degree relatives. Genetic testing was performed with a nine-gene panel ( ACD , BAP1 , CDK4 , CDKN2A , POT1 , TERT , TERF2IP , MC1R, and MITF ). In 36 patients, we identified 2 (5.6%) with germline pathogenic variants in CDKN2A and BAP1 and 4 (11.1%) with variants of uncertain significance in the high-penetrance genes. MC1R variants were found in 86.5%, and both red hair color variants and unknown risk variants were enriched in patients compared to a control group. The low frequency of germline pathogenic variants in the high-penetrance genes and the high prevalence of MC1R variants found in our cohort show the importance of the MC1R genotype in determining the risk of melanoma in the Brazilian melanoma-prone families. |
