title: A mutation and expression analysis of the oncogene BRAF in pituitary adenomas.
abstract: OBJECTIVE
  BRAF is an oncogene that is commonly mutated in both melanomas and papillary thyroid carcinomas, usually at position V600E that leads to constitutive activity in the Ras-mitogen-activated protein kinase (MAPK) pathway. We speculated that this same gene may be either mutated at this site, or overexpressed, in pituitary adenomas.
  
  
  METHODS
  We sequenced 37 pituitary adenomas for a mutation at the V600E position. In addition, we investigated B-Raf mRNA expression in normal pituitary (n = 5) and nonfunctioning pituitary adenomas (NFPA) (n = 6) by semiquantitative PCR, and in a further 27 pituitary adenomas of various types and 10 normal pituitaries using real-time quantitative PCR. Finally, we explored B-Raf protein expression in 10 normal pituitaries and 12 NFPAs.
  
  
  RESULTS
  No sequence mutations for the substitution V600E were identified. B-Raf mRNA was overexpressed in pituitary adenomas compared to normal pituitary, and this was entirely due to overexpression in NFPAs. NFPAs also showed very variable expression of B-Raf protein, but those tumours showing highest levels of B-Raf mRNA expressed the most B-Raf protein.
  
  
  CONCLUSIONS
  Mutations previously seen in the majority of melanomas and a substantial minority of papillary thyroid carcinomas are not a frequent finding in pituitary adenomas. However, overexpression of B-Raf mRNA and protein may be a feature of NFPAs, highlighting overactivity of the Ras-B-Raf-MAP kinase pathway in these tumours.
authors.affiliation: Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Ewing
authors.forename: Stephen
authors.initials: S
authors.lastname: Pedder-Smith
authors.forename: Giulia
authors.initials: G
authors.lastname: Franchi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.forename: Michelle
authors.initials: M
authors.lastname: Emery
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vax
authors.forename: Edwin
authors.initials: E
authors.lastname: Garcia
authors.forename: Sándor
authors.initials: S
authors.lastname: Czirják
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hanzély
authors.forename: Blerina
authors.initials: B
authors.lastname: Kola
authors.forename: Márta
authors.initials: M
authors.lastname: Korbonits
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000737:chemistry; D000236:Adenoma / Q000737:chemistry*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000737:chemistry; D006801:Humans; D010911:Pituitary Neoplasms / Q000737:chemistry*; D016133:Polymerase Chain Reaction / Q000379:methods; D015175:Prolactinoma / Q000737:chemistry; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D018709:Statistics, Nonparametric
chemical_list: D012333:RNA, Messenger; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf