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: Elke Hacker, Eduardo Nagore, Lorenzo Cerroni, Susan L Woods, Nicholas K Hayward, Brett Chapman, Grant W Montgomery, H Peter Soyer, David C Whiteman
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 133 Issue 4 Pg. 1027-33 (Apr 2013) ISSN: 1523-1747 [Electronic] United States
• PMID: 23096702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Receptor, Melanocortin, Type 1
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• GTP Phosphohydrolases
• NRAS protein, human

Topics

• Austria (epidemiology)
• Female
• GTP Phosphohydrolases (genetics)
• Gene Frequency
• Genetic Predisposition to Disease (epidemiology, genetics)
• Genotype
• Humans
• Male
• Melanoma (epidemiology, genetics)
• Membrane Proteins (genetics)
• Middle Aged
• Phenotype
• Proto-Oncogene Proteins B-raf (genetics)
• Receptor, Melanocortin, Type 1 (genetics)
• Skin Neoplasms (epidemiology, genetics)
• Spain (epidemiology)