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

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

Vitis vinifera Tannat, the result of a multidisciplinary research

Tema del mesLa calidad de la uva, y por tanto del vino, es el resultado de la interacción de numerosos factores que involucran aspectos biológicos (variedad, clon, portainjerto, estado sanitario), físicos (tipo de suelo y su manejo), climáticos (temperatura, pluviometría, luz) y culturales (densidad de plantación, conducción, poda, carga de fruta, manejo de la vegetación, fertilización). La conjunción y el manejo armónico de estos factores condicionarán las potencialidades de un viñedo y determinará la cantidad de fruta capaz de soportar la planta. Los viticultores uruguayos han buscado incidir en estos aspectos reemplazando las viejas plantas Tannat por nuevos clones comerciales de esta variedad. Para intentar evaluar el impacto de esta decisión, nuestro grupo evaluó las relaciones genéticas entre los clones Tannat antiguos, presentes en Uruguay, y los clones comerciales franceses, introducidos recientemente. Los resultados demostraron que los clones analizados representan un pool genéticamente uniforme, donde se pueden discriminar dos grupos mediante marcadores moleculares y por la composición de componentes volátiles unidos a azúcares (glicósidos). Este aspecto es desafiante, ya que una de las características económicas más significativas de cultivar es el aroma que la uva puede impartirle al vino, ya que los constituyentes volátiles de la uva son responsables de los principales aromas del mosto y proveen las bases del carácter varietal. La calidad de un vino también es consecuencia de los procesos de fermentación (alcohólica y maloláctica). La fermentación aumenta la complejidad aromática del vino, ayudando en la extracción de los sólidos del mosto, modificando compuestos derivados de la uva y produciendo una importante cantidad de compuestos aromáticos (alcoholes, ésteres, ácidos, aldehídos). Aunque estos compuestos pueden encontrarse en muchos vinos, el tipo de proceso ejecutado puede causar cambios importantes en sus concentraciones. Para el vino Tannat esto se evaluó estudiando el perfil aromático por análisis sensorial y por análisis químico, utilizando una separación cromatográfica con jueces capaces de percibir el aroma de los componentes separados (olfatomería). Los vinos tintos Tannat también poseen contenidos elevados de taninos y un color intenso, características responsables de la originalidad de estos vinos. Las correlaciones entre las diferentes familias de pigmentos estudiados por técnicas separativas y espectroscópicas y parámetros que definen las notas de color (CIELAB), revelaron la importancia de las variaciones encontradas en antocianos, flavanol-antocianos y piranoantocianinas en el color y palatabilidad de estos vinos. El enfoque presentado muestra la integración multidisciplinaria que define nuestro grupo, que busca aportar herramientas objetivas para aplicar el concepto genérico de “Enología de Mínima Intervención” a la producción de vinos Tannat.The quality of the grapes, and thus the wine, is the result of the interaction of many factors involving biological (variety, clone, rootstock and sanitary status), physical (soil type and its management), climate (temperature, rainfall, light) and cultural (planting density, canopy management, ripening, fruit load, fertilization). The effect produced by the sum of these factors, and their control, will condition the potential of a vineyard determining the amount of fruit capable of supporting the plant. The Uruguayan winemakers have intended to influence on this situation for the Vitis vinifera cv Tannat, replacing the old plants by new commercially available clones of this variety. In order to assess the impact of this decision, our research group studied the genetic relationships among the old Tannat clones present in Uruguay, and the French commercial ones recently introduced. The results demonstrated that the clones evaluated represent a genetically uniform pool, where two groups can be discriminated using both molecular markers and the composition of glicosylated aroma compounds. This aspect has a particular relevance as the scent that the grape can impart to the wine represents one of the most significant economic characteristics of a cultivar. Secondary metabolites from grapes are responsible for the main must aromatic constituents providing the basis of the varietal character. The wine quality is also a result of the fermentation processes (alcoholic and malolactic). The fermentations increase the wine aromatic complexity, assisting the removal of solids from the must and produce chemical modifications on those compounds derived from grapes producing a significant amount of metabolites (alcohols, esters, acids, aldehydes). Although these compounds can be found in many wines, the kind of process executed can cause major changes in their concentrations. These aspects were studied on Tannat wines studying their flavor profile using different approaches: descriptive sensory analysis, chemical analysis and gas chromatographyolfactometry. Tannin contents and the intense color of Tannat red wines are also features responsible for the originality of these wines. The correlations between the different pigment families studied by separation and spectroscopic tools and CIELAB parameters revealed the importance of the variations found in anthocyanins, flavanol-anthocyanins, pyranoanthocyanins fractions and the color and palatability of these wines. The results above presented shows the multidisciplinary integration that defines our group, which seeks to provide objective tools to implement the generic concept of “Minimum Intervention Oenology” to produce Tannat wines

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

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.GenoMEL, National Cancer Institute of the US National Institutes of Health, Fondo de Investigaciones Sanitarias, CIBER de Enfermedades Raras of the Instituto de Salud Carlos II, Catalan Government, European Commission, Instituto de Salud Carlos III, Consejo Nacional de Ciencia y Tecnologia (CONACYT), Fundacao para o Amparo da Pesquisa do Estado de Sao Paulo (FAPESP), Brazilian Post-Graduation Agency Capes (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), Comision Honoraria de Lucha Contra el Cancer and Fundacion Manuel Perez, Montevide