title: [Genotypic hypervariability of melanoma: a therapeutic challenge].
abstract: Cutaneous melanoma remains a management challenge. Melanoma is the leading cause of death from skin tumors worldwide. Melanoma progression is well defined in its clinical, histopathological and biological aspects, but the molecular mechanism involved and the genetic markers associated to metastatic dissemination are only beginning to be defined. The recent development of high-throughput technologies aimed at global molecular profiling of cancer is switching on the spotlight at previously unknown candidate genes involved in melanoma. Among those genes, BRAF is one of the most supposed to be of interest and targeted therapies are ongoing in clinical trials. In familial melanoma, germline mutations in two genes, CDKN2A and CDK4, that play a pivotal role in controlling cell cycle and division. It is hope that this better understanding of the biologic features of melanoma and the mechanisms underlying tumor-induced immunosuppression will lead to efficaceous targeted therapy.
authors.affiliation: Service de Dermatologie, Hôpital de l'Hôtel-Dieu, Lyon, France. stephane.dalle@chu-lyon.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dalle
authors.forename: Tanguy
authors.initials: T
authors.lastname: Martin-Denavit
authors.forename: Luc
authors.initials: L
authors.lastname: Thomas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D015195:Drug Design; D005602:France / Q000453:epidemiology; D019942:Genes, p16; D016158:Genes, p53; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation; D009362:Neoplasm Metastasis; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000502:physiology; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D044102:Receptor, Melanocortin, Type 1; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human