title: Analysis of the BRAFV600E mutation in 19 cases of Langerhans cell histiocytosis in Japan.
abstract: Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal proliferation of CD1a- and CD207 (langerin)-positive dendritic cells. Mutated BRAF (p.V600E) is observed in histiocyte-related diseases and dendritic cell-related diseases, including LCH. BRAFV600E is observed in some LCH cases and is thought to be involved in maintaining MAPK activation. We retrospectively analyzed BRAFV600E in 19 patients diagnosed with LCH. In our study, direct sequencing for exon 15, a mutation hotspot, demonstrated that 4 out of the 19 patients (21%) harbored a GTG > GAG (valine > glutamic acid) base substitution, which encodes BRAFV600E. The clinical impact of BRAFV600E in such diseases is unclear. The frequency of BRAFV600E in our LCH patients from Japan was lower than that reported in the United States and in Germany. However, reports from Asia tend to show a lower rate of the BRAFV600E mutation. These results imply the possibility of different genetic backgrounds in the pathogenesis of LCH across various ethnicities. We also performed an immunohistochemical analysis to detect BRAFV600E using the mutation-specific monoclonal antibody. However, immunohistochemical analysis failed to detect any mutated protein in any of the 4 BRAFV600E-positive cases. This implies that at present, BRAFV600E should be assessed by direct sequencing. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.|Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Kurume, Fukuoka, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koga
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurita
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.|Department of Pathology, Nagasaki University, School of Medicine, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Seto
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D015415:Biomarkers; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003062:Codon; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003062:Codon; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAFV600E; Japan; Langerhans cell histiocytosis