title: Histologic and Phenotypic Factors and MC1R Status Associated with BRAF(V600E), BRAF(V600K), and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas.
abstract: Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports.
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Queensland, Australia.
authors.forename: Elke
authors.initials: E
authors.lastname: Hacker
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Olsen
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Kvaskoff
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pandeya
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Abrey
authors.initials: A
authors.lastname: Yeo
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Cancer Research UK Manchester Institute & University of Manchester, Manchester, UK.
authors.forename: Adèle C
authors.initials: AC
authors.lastname: Green
authors.affiliation: Anatomical Pathology, Sullivan Nicolaides Pathology, Taringa, Queensland, Australia.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Williamson
authors.affiliation: Anatomical Pathology, IQ Pathology, West End, Queensland, Australia.
authors.forename: Joe
authors.initials: J
authors.lastname: Triscott
authors.affiliation: Anatomical Pathology, IQ Pathology, West End, Queensland, Australia.
authors.forename: Dominic
authors.initials: D
authors.lastname: Wood
authors.affiliation: Anatomical Pathology, Queensland Medical Laboratory, Murarrie, Queensland, Australia.
authors.forename: Rohan
authors.initials: R
authors.lastname: Mortimore
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.affiliation: Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: David.Whiteman@qimrberghofer.edu.au.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D005192:Family Health; D005260:Female; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D055623:Keratosis, Actinic / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D013472:Sunlight / Q000009:adverse effects; D011795:Surveys and Questionnaires; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D004273:DNA, Neoplasm; D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins