title: High frequency of BRAF mutations in nevi.
abstract: To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Pollock
authors.forename: Ursula L
authors.initials: UL
authors.lastname: Harper
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Hansen
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yudt
authors.forename: Mitchell
authors.initials: M
authors.lastname: Stark
authors.forename: Christiane M
authors.initials: CM
authors.lastname: Robbins
authors.forename: Tracy Y
authors.initials: TY
authors.lastname: Moses
authors.forename: Galen
authors.initials: G
authors.lastname: Hostetter
authors.forename: Urs
authors.initials: U
authors.lastname: Wagner
authors.forename: John
authors.initials: J
authors.lastname: Kakareka
authors.forename: Ghadi
authors.initials: G
authors.lastname: Salem
authors.forename: Tom
authors.initials: T
authors.lastname: Pohida
authors.forename: Peter
authors.initials: P
authors.lastname: Heenan
authors.forename: Paul
authors.initials: P
authors.lastname: Duray
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D009506:Nevus / Q000235:genetics* / Q000473:pathology; D027384:Oncogene Proteins v-raf / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D027384:Oncogene Proteins v-raf