title: MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma.
abstract: Recent therapeutic advances have improved melanoma patientś clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild-type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Elias
authors.initials: E
authors.lastname: Orouji
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Orouji
authors.affiliation: Institute of Pathology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Gaiser
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Lionel
authors.initials: L
authors.lastname: Larribère
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Utikal
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; ERK; MEK; NRAS; melanoma