Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

Abstract

Purpose:CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America.Genet Med 18 7, 727–736.Methods:CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained.Genet Med 18 7, 727–736.Results:Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients.Genet Med 18 7, 727–736.Conclusion:The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727–736.

Hereditary melanoma: a five-year study of Brazilian patients in a cancer referral center - phenotypic characteristics of probands and pathological features of primary tumors

“…However, in areas with a moderate to high incidence of melanomas, FMS is diagnosed in individuals with three or more primary melanomas and in families with three or more cases of melanomas in first- or second-degree relatives. 5 - 8 …”

Genome-wide linkage analysis in Spanish melanoma-prone families identifies a new familial melanoma susceptibility locus at 11q

“…In Spain, the genetic background in melanoma-prone families remains unknown in >80% of families [5,6].…”

“…In the Mediterranean population, due to the low incidence of the disease, melanoma-prone families are considered as those with at least two melanoma patients in firstor second-degree relatives [3,4]. Overall, 14% of Spanish melanoma-prone families carry CDKN2A pathogenic variants, with prevalence increasing with the number of cases in the family: 11% in families with 2 cases, 23% in families with 3 cases, and 36-43% in families with at least 4 melanoma cases [5,6].…”

Identification of CDKN2A variants in breast cancer patients in Pakistan

“…Mutations in or functional inactivation of CDKN2A are known to be involved in numerous types of human cancers, such as leukaemia, lung cancer, oesophageal cancer, glioma, breast cancer and melanoma (Hinshelwood et al, 2009;McKenzie et al, 2010;Puig et al, 2016). It is primarily a melanoma-associated gene and mutations have been reported in 24% of melanoma-prone Latin America families (Puig et al, 2016). Similarly, 14% of Spanish melanoma patients also harbour CDKN2A variants (Puig et al, 2016).…”

“…It is primarily a melanoma-associated gene and mutations have been reported in 24% of melanoma-prone Latin America families (Puig et al, 2016). Similarly, 14% of Spanish melanoma patients also harbour CDKN2A variants (Puig et al, 2016). However, CDKN2A has shown no clear association with breast cancer in several other populations or ethnic groups (Berns et al, 1995;Quesnel et al, 1995;Horcasitas et al, 2017;Aftab et al, 2019).…”