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Puig S.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | Puig S.,University of Barcelona | Potrony M.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | Cuellar F.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | And 46 more authors.
Genetics in Medicine

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. © American College of Medical Genetics and Genomics. Source

Pozzobon F.C.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | Pozzobon F.C.,National University of Colombia | Puig-Butille J.A.,Centro Investigacion Biomedica En Red Of Enfermedades Raras Ciberer | Puig-Butille J.A.,IDIBAPS Institute dInvestigacions Biomediques August Pi i Sunyer | And 16 more authors.
British Journal of Dermatology

Background The identification of BRAF mutations in melanoma led to the development and implementation of new and effective therapies. Few clinical and histological features have been associated with this mutational status. Objectives The main objective of this study was to investigate clinical, histopathological and dermoscopic characteristics of primary melanomas according to BRAF or NRAS mutational status. Methods An observational retrospective study including melanoma dermoscopy images assessed for somatic mutations in BRAF and NRAS. Results Seventy-two patients were included, 30 women (42%) and 42 men (58%), mean age was 59 ± 15·51 years. BRAF-mutated melanomas were more frequently located on the trunk (n = 18, 64% for BRAF-mutated vs. n = 11, 29% for wild-type melanomas, P = 0·013). Histological ulceration was associated with the presence of BRAF mutations [odds ratio (OR) 3·141; 95% confidence interval (CI) 1·289-7·655; P = 0·002]. The Breslow index tended to be thicker in BRAF-mutated compared with wild-type (P = 0·086). BRAF mutations were present in 28 (39%) patients and only four cases were positive for NRAS mutations (6%), BRAF and NRAS mutations being mutually exclusive. The presence of dermoscopic peppering was associated with MAPK mutations (BRAF and NRAS) (OR 1·68; 95% CI 1·089-2·581; P = 0·015). Dermoscopic ulceration was also associated with BRAF mutations excluding acral and facial melanomas (OR 2·64; 95% CI 1·032-6·754). Conclusions This study showed a correlation between BRAF and NRAS status and dermoscopic findings of 'peppering' as an expression of regression and melanophages in the dermis, suggesting a morphological consequence of immune behaviour in BRAF-mutated melanomas. What's already known about this topic? Knowledge of BRAF or NRAS mutations has allowed the development and implementation of new therapeutic options. Mutation status has been related to clinical and histological features. What does this study add? The results show an association between dermoscopic regression such as blue-grey peppering in BRAF- and NRAS-mutated melanomas, which could be a result of their immune morphological behaviour. The presence of dermoscopic and histopathological ulceration was also related to BRAF-mutated melanomas. © 2014 British Association of Dermatologists. Source

Puig-Butille J.A.,Centro InvestigaciInvestigacion Biomedica en Enfermedades Raras CIBERER | Puig-Butille J.A.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | Badenas C.,Centro InvestigaciInvestigacion Biomedica en Enfermedades Raras CIBERER | Badenas C.,Hospital Clinic and IDIBAPS Institute DInvestigacions Biomediques August Pi i Sunyer | And 9 more authors.
Experimental Dermatology

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS-related pathways are present in 87.5% of acral lentiginous melanomas. © 2012 John Wiley & Sons A/S. Source

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