title: BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma.
abstract: BRAF oncogenic mutations have been identified in significant numbers of melanocytic lesions. To correlate BRAF mutation and melanoma progression, we screened BRAF mutations in 65 melanocytic lesions, including nevi, radial growth phase (RGP), vertical growth phase (VGP) melanomas, and melanoma metastases, as well as 25 melanoma cell lines. PCR and direct sequencing were used to analyze DNA samples extracted from laser capture microdissected tissues. A similar high frequency (62-72%) of BRAF oncogenic mutations was identified in melanocytic nevi, VGP, metastatic melanomas, and melanoma cell lines [H. Davies et al., Nature (Lond.), 417: 949-954, 2002; P. M. Pollock et al., Nat. Genet., 33: 19-20, 2002; and M. S. Brose et al., Cancer Res., 62: 6997-7000, 2002]. In striking contrast, we found BRAF lesions in only 10% of the earliest stage or RGP melanomas. These findings imply that BRAF mutations cannot be involved in the initiation of the great majority of melanomas but instead reflect a progression event with important prognostic implications in the transition from the great majority of RGP melanomas to VGP and/or metastatic melanoma.
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Jianli
authors.initials: J
authors.lastname: Dong
authors.forename: Robert G
authors.initials: RG
authors.lastname: Phelps
authors.forename: Rui
authors.initials: R
authors.lastname: Qiao
authors.forename: Shen
authors.initials: S
authors.lastname: Yao
authors.forename: Outhiriaradjou
authors.initials: O
authors.lastname: Benard
authors.forename: Zeev
authors.initials: Z
authors.lastname: Ronai
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Aaronson
mesh_terms: D018450:Disease Progression; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009508:Nevus, Pigmented / Q000235:genetics / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D015513:Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf