40 research outputs found
Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case series
Spitzoid morphology in familial melanoma has been associated with germline variants in
POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid
differentiation. The aim is to assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD,
TERF2IP, and TERT ) commonly exhibit spitzoid morphology.Medicin
Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV)
El diagnĂłstico y tratamiento del melanoma en atenciĂłn especializada es un campo en el que se han producido numerosos cambios. El objetivo de esta guĂa es ofrecer a los dermatĂłlogos españoles una referencia para resolver las dudas clĂnicas mĂĄs frecuentes basĂĄndose en la evidencia actual. Para la realizaciĂłn de esta guĂa se escogiĂł a miembros del Grupo Español de Dermato-OncologĂa y CirugĂa con experiencia en el tratamiento de estos tumores y con interĂ©s en participar en la elaboraciĂłn de la guĂa. Se hizo una adaptaciĂłn de las guĂas de prĂĄctica clĂnica existentes mediante el mĂ©todo ADAPTE: inicialmente se resumiĂł el proceso de atenciĂłn y se elaboraron las preguntas clĂnicas relevantes. Se seleccionaron las guĂas mejor puntuadas mediante el instrumento AGREE II, realizando la bĂșsqueda de las respuestas en dichas guĂas y elaborando las recomendaciones. Finalmente se sometiĂł la guĂa a revisiĂłn externa. La guĂa se estructurĂł a partir de 21 preguntas clĂnicas que fueron seleccionadas por su relevancia, dado que se centran en aspectos que pueden plantear decisiones difĂciles en el manejo del melanoma, y se han respondido empleando la evidencia obtenida de las mejores guĂas existentes. Entre las limitaciones de esta guĂa merece reseñarse que la evidencia es escasa para responder a algunas preguntas. En algunos aspectos el cambio es rĂĄpido y exige una actualizaciĂłn frecuente de la guĂa. Esta guĂa responde a preguntas habituales sobre el manejo del melanoma en la prĂĄctica clĂnica diaria, sirviendo a los dermatĂłlogos como referencia en la toma de decisiones, siempre teniendo presente los recursos y preferencias del paciente
InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma
We are conducting a multicenter study to identify classifiers predictive of disease-specific
survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor
samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID
patients. We also evaluated tissue-derived predictors of extracted nucleic acidsâ quality and
success in downstream testing. This ongoing study will target 1,000 melanomas within the
international InterMEL consortium.Medicin
Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT
Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling
Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project
Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev
Frequency and characteristics of familial melanoma in Spain: The FAM-GEM-1 Study
Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior
A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date
Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies
Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields