title: BRAF, KIT and NRAS mutations and expression of c-KIT, phosphorylated extracellular signal-regulated kinase and phosphorylated AKT in Japanese melanoma patients.
abstract: To clarify the status of gene mutation and activation of growth signal in melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15, NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by laser capture microdissection, and performed direct sequencing in 20 cases of acral lentiginous melanoma (ALM) and 17 cases of superficial spreading melanoma (SSM). In the study of the mutation of BRAF, pyrosequencing was also done. To examine the cell proliferation signaling, immunohistochemistry for phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated AKT (phosphorylated AKT) and c-KIT was done. The mutation of BRAF p.V600E was detected in 13 cases of ALM (65.0%) and 12 cases of SSM (70.6%). No NRAS mutation was found in all cases. The mutation in exons 9, 11, and 18 of KIT was detected in nine cases. The mutation of BRAF and KIT showed no correlation with clinical stage, lymph node metastasis, tumor thickness, ulceration and histology. pERK and pAKT was observed in small population of melanoma cells and there was no correlation with gene mutation. Our results indicate that the mutations of BRAF and KIT exist in Japanese melanoma patients, however, the cell growth signaling may be regulated by not only these mutated genes, but by other unknown regulatory factors, which may affect the prognosis of melanoma.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Oyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Funasaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawana
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Saeki
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005091:Exons / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D005260:Female; D011905:Genes, ras; D006801:Humans; D007564:Japan; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010766:Phosphorylation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BRAF; KIT; melanoma; phosphorylated AKT; phosphorylated extracellular signal-regulated kinase