Dataset Information

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.

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.

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.

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.

SUBMITTER: Puig S

PROVIDER: S-EPMC4940430 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Puig Susana S Potrony Miriam M Cuellar Francisco F Puig-Butille Joan Anton JA Carrera Cristina C Aguilera Paula P Nagore Eduardo E Garcia-Casado Zaida Z Requena Celia C Kumar Rajiv R Landman Gilles G Costa Soares de Sá Bianca B Gargantini Rezze Gisele G Facure Luciana L de Avila Alexandre Leon Ribeiro AL Achatz Maria Isabel MI Carraro Dirce Maria DM Duprat Neto João Pedreira JP Grazziotin Thais C TC Bonamigo Renan R RR Rey Maria Carolina W MC Balestrini Claudia C Morales Enrique E Molgo Montserrat M Bakos Renato Marchiori RM Ashton-Prolla Patricia P Giugliani Roberto R Larre Borges Alejandra A Barquet Virginia V Pérez Javiera J Martínez Miguel M Cabo Horacio H Cohen Sabban Emilia E Latorre Clara C Carlos-Ortega Blanca B Salas-Alanis Julio C JC Gonzalez Roger R Olazaran Zulema Z Malvehy Josep J Badenas Celia C

Genetics in medicine : official journal of the American College of Medical Genetics 20151217 7

<h4>Purpose</h4>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.<h4>Methods</h4>CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uru ...[more]

PMID: 26681309

Similar Datasets

Project description:BACKGROUND:Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico. RESULTS:We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population's genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects. CONCLUSIONS:Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

Similar Datasets

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