title: BRAF point mutations in primary melanoma show different prevalences by subtype.
abstract: To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.
authors.affiliation: Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Chunbo
authors.initials: C
authors.lastname: Niu
authors.forename: Rui
authors.initials: R
authors.lastname: Makino
authors.forename: Chieko
authors.initials: C
authors.lastname: Kudo
authors.forename: Chunlan
authors.initials: C
authors.lastname: Sun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Jun
authors.initials: J
authors.lastname: Matsunaga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hachiro
authors.initials: H
authors.lastname: Tagami
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.forename: Akira
authors.initials: A
authors.lastname: Horii
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D017354:Point Mutation; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf