title: BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival.
abstract: Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.
authors.affiliation: The Gade Institute, Section of Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway. lars.akslen@gades.uib.no
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.forename: Oddbjørn
authors.initials: O
authors.lastname: Straume
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bachmann
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D002455:Cell Division; D005500:Follow-Up Studies; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D018807:Polymorphism, Single-Stranded Conformational; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf