The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population.
There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.
Hacker
Elke
E
Genetics & Population Health Division, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. Elke.Hacker@qimr.edu.au
Hayward
Nicholas K
NK
Dumenil
Troy
T
James
Michael R
MR
Whiteman
David C
DC
D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D004781:Environmental Exposure; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / 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*; D013472:Sunlight
D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf