title: NRAS and BRAF mutations in cutaneous melanoma and the association with MC1R genotype: findings from Spanish and Austrian populations.
abstract: There is increasing epidemiologic and molecular evidence that cutaneous melanomas arise through multiple causal pathways. To further define the pathways to melanoma, we explored the relationship between germline and somatic mutations in a series of melanomas collected from 134 Spanish and 241 Austrian patients. Tumor samples were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed clinical data were systematically collected from patients. We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk. We observed a nonsignificant association between germline MC1R status and somatic BRAF mutations in melanomas from trunk sites (odds ratio (OR) 1.8 (0.8-4.1), P=0.1), whereas we observed a significant inverse association between MC1R and BRAF for melanomas of the head and neck (OR 0.3 (0.1-0.8), P=0.02). This trend was observed in both the Spanish and Austrian populations.
authors.affiliation: Genetics and Computational Biology Department, Queensland Institute of Medical Research, Brisbane, Queensland, Australia .
authors.forename: Elke
authors.initials: E
authors.lastname: Hacker
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nagore
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerroni
authors.forename: Susan L
authors.initials: SL
authors.lastname: Woods
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Brett
authors.initials: B
authors.lastname: Chapman
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: H Peter
authors.initials: HP
authors.lastname: Soyer
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
mesh_terms: D001317:Austria / Q000453:epidemiology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D000096142:Cutaneous Malignant Melanoma
chemical_list: D008565:Membrane Proteins; D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human