Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 31;24(21):15830.
doi: 10.3390/ijms242115830.

Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients

Bianca Costa Soares de Sá  1 , Luciana Facure Moredo  1 , Giovana Tardin Torrezan  2   3 , Felipe Fidalgo  2 , Érica Sara Souza de Araújo  2 , Maria Nirvana Formiga  4 , João Pereira Duprat  1 , Dirce Maria Carraro  2   3
Affiliations

Characterization of Potential Melanoma Predisposition Genes in High-Risk Brazilian Patients

Bianca Costa Soares de Sá et al. Int J Mol Sci. .

Abstract

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.

Keywords: familial melanoma; germline pathogenic variants; melanoma predisposition; melanoma susceptibility; multiple primary neoplasms.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Pedigrees of the probands that showed genetic variants in the high-penetrance genes. (A) Pedigree of FM patient (MH11) carrying the GPV in CDKN2A, VUS in ACD gene and classified as r/0 for MC1R. (B) Pedigree of MPM patient (MH20) carrying the GPV in BAP1 and classified as R/0 for MC1R. (C) Pedigree of FM patient (MH32) carrying the other VUS in ACD gene and classified as r/0 for MC1R. (D) Pedigree of FM patient (MH28) carrying the VUS in TERT gene and classified as u/0 for MC1R. (E) Pedigree of FM patient (MH16) carrying the VUS in POT1 gene and classified as R/u for MC1R.
See this image and copyright information in PMC

References

    1. Berwick M., Erdei E., Hay J. Melanoma epidemiology and public health. Dermatol. Clin. 2009;27:205–214. doi: 10.1016/j.det.2008.12.002. - DOI - PMC - PubMed
    1. Psaty E.L., Scope A., Halpern A.C., Marghoob A.A. Defining the patient at high risk for melanoma. Int. J. Dermatol. 2010;49:362–376. doi: 10.1111/j.1365-4632.2010.04381.x. - DOI - PubMed
    1. Read J., Wadt K.A., Hayward N.K. Melanoma genetics. J. Med. Genet. 2016;53:1–14. doi: 10.1136/jmedgenet-2015-103150. - DOI - PubMed
    1. Hansen C.B., Wadge L.M., Lowstuter K., Boucher K., Leachman S.A. Clinical germline genetic testing for melanoma. Lancet Oncol. 2004;5:314–319. doi: 10.1016/S1470-2045(04)01469-X. - DOI - PubMed
    1. Leachman S.A., Carucci J., Kohlmann W., Banks K.C., Asgari M.M., Bergman W., Bianchi-Scarrà G., Brentnall T., Paillerets B.B.-D., Bruno W., et al. Selection criteria for genetic assessment of patients with familial melanoma. J. Am. Acad Dermatol. 2009;61:677.e1–677.e14. doi: 10.1016/j.jaad.2009.03.016. - DOI - PMC - PubMed

Substances