High frequency of BRAF mutations in nevi.
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.
Pollock
Pamela M
PM
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA.
Harper
Ursula L
UL
Hansen
Katherine S
KS
Yudt
Laura M
LM
Stark
Mitchell
M
Robbins
Christiane M
CM
Moses
Tracy Y
TY
Hostetter
Galen
G
Wagner
Urs
U
Kakareka
John
J
Salem
Ghadi
G
Pohida
Tom
T
Heenan
Peter
P
Duray
Paul
P
Kallioniemi
Olli
O
Hayward
Nicholas K
NK
Trent
Jeffrey M
JM
Meltzer
Paul S
PS
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
D027384:Oncogene Proteins v-raf