title: [Translational research and diagnostics of melanoma].
abstract: Although early stage malignant melanoma (MM) has a favorable prognosis five year survival rate is poor (<10%) in patients suffering from distant metastases. Due to molecular typing of MM recently high response rates were achieved in metastatic MM by using specific inhibitors directed against the mutated form of BRAF kinase, e.g. Vemurafinib and Dabrafinib. Therefore BRAF mutation analysis has become standard of care in advanced MM and pathologists are urged to provide a quality guaranteed molecular diagnostics. However, squamous neoplasias (e. g., keratoacanthomas) and recurrences of MM mostly within 6 months during targeted therapy point to the need of further translational research. Thus new drugs, such as MEK inhibitors, based on the MAP-kinase pathway downstream of BRAF have already effectively been used. Finally, the impact of molecular characteristics in different subtypes of MM (acral, mucosal, uveal) will be discussed with respect to their specific mutational spectrum (e.g. cKIT , NRAS , GNAQ).
authors.affiliation: Institut für Pathologie Nordhessen, Germaniastr. 7, 34119 Kassel. rueschoff@patho-nordhessen.de
authors.forename: J
authors.initials: J
authors.lastname: Rüschoff
authors.forename: M
authors.initials: M
authors.lastname: Kleinschmidt
authors.forename: P
authors.initials: P
authors.lastname: Middel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D010091:Oximes / Q000627:therapeutic use; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use; D057170:Translational Research, Biomedical; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D007093:Imidazoles; D007211:Indoles; D008565:Membrane Proteins; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C561627:dabrafenib