BACKGROUND: Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35-70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R. OBJECTIVES: To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay. METHODS: We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction-single strand conformational polymorphism analysis. The MC1R gene was sequenced. RESULTS: Mutations in CDKN2A were detected in five of six families: c.-34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families. CONCLUSIONS: The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range.
BACKGROUND:Familial melanoma, a cluster of several cases within a single family, accounts for approximately 10% of cases of melanoma. Hereditary melanoma is defined as two or more first-degree relatives having melanoma. A member of a melanoma-prone family has a 35-70-fold increased relative risk of developing a melanoma. Genetic susceptibility is linked to the major susceptibility genes CDKN2A and CDK4, and the minor susceptibility gene MC1R. OBJECTIVES: To determine the clinical and genetic characteristics of cutaneous melanoma in melanoma-prone families from Uruguay. METHODS: We studied 13 individuals from six melanoma-prone families living in Uruguay. Phenotype, familial and personal history were recorded. Molecular screening of CDKN2A and CDK4 was done by polymerase chain reaction-single strand conformational polymorphism analysis. The MC1R gene was sequenced. RESULTS: Mutations in CDKN2A were detected in five of six families: c.-34G>T, p.G101W and p.E88X. A novel germline mutation p.E88X, associated with hereditary melanoma in two unrelated families, is described. We hypothesize that a founder effect occurred probably in the Mediterranean region. No mutations in CDK4 were detected. Six different MC1R variants, all previously reported, were present in Uruguayan families. CONCLUSIONS: The overall rate of deleterious CDKN2A mutations in our familial melanoma pedigrees, even though the sample size is small, was considerably higher (83%) than the often quoted range.
Authors: Alexandre Leon Ribeiro de Ávila; Ana Cristina Victorino Krepischi; Luciana Facure Moredo; Talita Ferreira Marques Aguiar; Felipe Carneiro da Silva; Bianca Costa Soares de Sá; Amanda França de Nóbrega; Maria Isabel Waddington Achatz; João Pedreira Duprat; Gilles Landman; Dirce Maria Carraro Journal: Fam Cancer Date: 2014-12 Impact factor: 2.375
Authors: Miriam Potrony; Celia Badenas; Paula Aguilera; Joan Anton Puig-Butille; Cristina Carrera; Josep Malvehy; Susana Puig Journal: Ann Transl Med Date: 2015-09
Authors: Mark Harland; Anne E Cust; Celia Badenas; Yu-Mei Chang; Elizabeth A Holland; Paula Aguilera; Joanne F Aitken; Bruce K Armstrong; Jennifer H Barrett; Cristina Carrera; May Chan; Joanne Gascoyne; Graham G Giles; Chantelle Agha-Hamilton; John L Hopper; Mark A Jenkins; Peter A Kanetsky; Richard F Kefford; Isabel Kolm; Johanna Lowery; Josep Malvehy; Zighereda Ogbah; Joan-Anton Puig-Butille; Jordi Orihuela-Segalés; Juliette A Randerson-Moor; Helen Schmid; Claire F Taylor; Linda Whitaker; D Timothy Bishop; Graham J Mann; Julia A Newton-Bishop; Susana Puig Journal: Hered Cancer Clin Pract Date: 2014-11-20 Impact factor: 2.857
Authors: Susana Puig; Miriam Potrony; Francisco Cuellar; Joan Anton Puig-Butille; Cristina Carrera; Paula Aguilera; Eduardo Nagore; Zaida Garcia-Casado; Celia Requena; Rajiv Kumar; Gilles Landman; Bianca Costa Soares de Sá; Gisele Gargantini Rezze; Luciana Facure; Alexandre Leon Ribeiro de Avila; Maria Isabel Achatz; Dirce Maria Carraro; João Pedreira Duprat Neto; Thais C Grazziotin; Renan R Bonamigo; Maria Carolina W Rey; Claudia Balestrini; Enrique Morales; Montserrat Molgo; Renato Marchiori Bakos; Patricia Ashton-Prolla; Roberto Giugliani; Alejandra Larre Borges; Virginia Barquet; Javiera Pérez; Miguel Martínez; Horacio Cabo; Emilia Cohen Sabban; Clara Latorre; Blanca Carlos-Ortega; Julio C Salas-Alanis; Roger Gonzalez; Zulema Olazaran; Josep Malvehy; Celia Badenas Journal: Genet Med Date: 2015-12-17 Impact factor: 8.822
Authors: Amelia K Smit; Marielys Collazo-Roman; Susan T Vadaparampil; Stella Valavanis; Jocelyn Del Rio; Brenda Soto; Idhaliz Flores; Julie Dutil; Peter A Kanetsky Journal: Sci Rep Date: 2020-04-29 Impact factor: 4.379
Authors: Joan Anton Puig-Butille; María José Escámez; Francisco Garcia-Garcia; Gemma Tell-Marti; Àngels Fabra; Lucía Martínez-Santamaría; Celia Badenas; Paula Aguilera; Marta Pevida; Joaquín Dopazo; Marcela del Río; Susana Puig Journal: Oncotarget Date: 2014-03-30