High frequency of BRAF mutations in nevi

PM Pollock, UL Harper, KS Hansen, LM Yudt, M Stark… - Nature …, 2003 - nature.com
PM Pollock, UL Harper, KS Hansen, LM Yudt, M Stark, CM Robbins, TY Moses, G Hostetter…
Nature genetics, 2003nature.com
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 …
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.
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