title: BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus.
abstract: OBJECTIVE
  The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting.
  
  
  METHODS
  A man in his 50s with Fitzpatrick skin type II presented with an irregularly pigmented melanocytic lesion on his back that met melanoma-specific dermoscopic criteria, and diagnostic shave excision of the lesion was performed. Histopathologic analysis revealed a melanoma in situ arising in a dysplastic nevus. Dermoscopy-targeted microbiopsy specimens were taken across the lesion, and genotyping was carried out on extracted DNA samples for BRAF and NRAS mutations. The melanoma in situ showed only BRAF wild-type results, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype.
  
  
  CONCLUSIONS
  Dermoscopy-targeted sampling and genotyping of a melanoma in situ arising in a dysplastic nevus revealed a phenotype-genotype paradox that confounds the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis. Further studies are required to investigate the importance of other candidate genes linked to melanomagenesis.
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Tan
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Lynlee L
authors.initials: LL
authors.lastname: Lin
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Australia3IQ Pathology, Brisbane, Queensland, Australia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Lambie
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Flewell-Smith
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Kasturee
authors.initials: K
authors.lastname: Jagirdar
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schaider
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: Tarl W
authors.initials: TW
authors.lastname: Prow
authors.affiliation: Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, Australia.
authors.forename: H Peter
authors.initials: HP
authors.lastname: Soyer
mesh_terms: D046169:Dermoscopy / Q000379:methods; D004416:Dysplastic Nevus Syndrome / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf