Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients
Increased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as <i>CDKN2A</i> and <i>CDK4</i>, risk variants in low- to moderate-penetrance genes (<i>MC1R</i> and <i>MITF</i>), and possibly...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/21/15830 |
| _version_ | 1797631799087595520 |
|---|---|
| author | Bianca Costa Soares de Sá Luciana Facure Moredo Giovana Tardin Torrezan Felipe Fidalgo Érica Sara Souza de Araújo Maria Nirvana Formiga João Pereira Duprat Dirce Maria Carraro |
| author_facet | Bianca Costa Soares de Sá Luciana Facure Moredo Giovana Tardin Torrezan Felipe Fidalgo Érica Sara Souza de Araújo Maria Nirvana Formiga João Pereira Duprat Dirce Maria Carraro |
| author_sort | Bianca Costa Soares de Sá |
| collection | DOAJ |
| description | Increased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as <i>CDKN2A</i> and <i>CDK4</i>, risk variants in low- to moderate-penetrance genes (<i>MC1R</i> and <i>MITF</i>), and possibly due to variants in emerging genes, such as <i>ACD</i>, <i>TERF2IP,</i> and <i>TERT</i>. 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 (<i>ACD</i>, <i>BAP1</i>, <i>CDK4</i>, <i>CDKN2A</i>, <i>POT1</i>, <i>TERT</i>, <i>TERF2IP</i>, <i>MC1R,</i> and <i>MITF</i>). In 36 patients, we identified 2 (5.6%) with germline pathogenic variants in <i>CDKN2A</i> and <i>BAP1</i> and 4 (11.1%) with variants of uncertain significance in the high-penetrance genes. <i>MC1R</i> 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 <i>MC1R</i> variants found in our cohort show the importance of the <i>MC1R</i> genotype in determining the risk of melanoma in the Brazilian melanoma-prone families. |
| first_indexed | 2024-03-11T11:28:50Z |
| format | Article |
| id | doaj.art-89c161a7c04a44a5b339c4a324933fd3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T11:28:50Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-89c161a7c04a44a5b339c4a324933fd32023-11-10T15:05:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124211583010.3390/ijms242115830Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian PatientsBianca Costa Soares de Sá0Luciana Facure Moredo1Giovana Tardin Torrezan2Felipe Fidalgo3Érica Sara Souza de Araújo4Maria Nirvana Formiga5João Pereira Duprat6Dirce Maria Carraro7Skin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, BrazilSkin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, BrazilClinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, BrazilClinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, BrazilClinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, BrazilOncogenetics Department, A.C. Camargo Cancer Center, São Paulo 01509-900, BrazilSkin Cancer Department, A.C. Camargo Cancer Center, São Paulo 01529-001, BrazilClinical and Functional Genomics Group, International Research Center/CIPE, A.C. Camargo Cancer Center, 440 Taguá St., São Paulo 01508-010, BrazilIncreased genetic risk for melanoma can occur in the context of germline pathogenic variants in high-penetrance genes, such as <i>CDKN2A</i> and <i>CDK4</i>, risk variants in low- to moderate-penetrance genes (<i>MC1R</i> and <i>MITF</i>), and possibly due to variants in emerging genes, such as <i>ACD</i>, <i>TERF2IP,</i> and <i>TERT</i>. 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 (<i>ACD</i>, <i>BAP1</i>, <i>CDK4</i>, <i>CDKN2A</i>, <i>POT1</i>, <i>TERT</i>, <i>TERF2IP</i>, <i>MC1R,</i> and <i>MITF</i>). In 36 patients, we identified 2 (5.6%) with germline pathogenic variants in <i>CDKN2A</i> and <i>BAP1</i> and 4 (11.1%) with variants of uncertain significance in the high-penetrance genes. <i>MC1R</i> 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 <i>MC1R</i> variants found in our cohort show the importance of the <i>MC1R</i> genotype in determining the risk of melanoma in the Brazilian melanoma-prone families.https://www.mdpi.com/1422-0067/24/21/15830familial melanomamelanoma predispositionmelanoma susceptibilitygermline pathogenic variantsmultiple primary neoplasms |
| spellingShingle | Bianca Costa Soares de Sá Luciana Facure Moredo Giovana Tardin Torrezan Felipe Fidalgo Érica Sara Souza de Araújo Maria Nirvana Formiga João Pereira Duprat Dirce Maria Carraro Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients International Journal of Molecular Sciences familial melanoma melanoma predisposition melanoma susceptibility germline pathogenic variants multiple primary neoplasms |
| title | Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients |
| title_full | Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients |
| title_fullStr | Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients |
| title_full_unstemmed | Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients |
| title_short | Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients |
| title_sort | characterization of potential melanoma predisposition genes in high risk brazilian patients |
| topic | familial melanoma melanoma predisposition melanoma susceptibility germline pathogenic variants multiple primary neoplasms |
| url | https://www.mdpi.com/1422-0067/24/21/15830 |
| work_keys_str_mv | AT biancacostasoaresdesa characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT lucianafacuremoredo characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT giovanatardintorrezan characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT felipefidalgo characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT ericasarasouzadearaujo characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT marianirvanaformiga characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT joaopereiraduprat characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients AT dircemariacarraro characterizationofpotentialmelanomapredispositiongenesinhighriskbrazilianpatients |