A mutation and expression analysis of the oncogene BRAF in pituitary adenomas

• Published in: Clinical endocrinology (Oxford) 2007-03, Vol.66 (3), p.348-352
• Main Authors: Ewing, Iain, Pedder-Smith, Stephen, Franchi, Giulia, Ruscica, Massimiliano, Emery, Michelle, Vax, Vladimir, Garcia, Edwin, Czirják, Sándor, Hanzély, Zoltán, Kola, Blerina, Korbonits, Márta, Grossman, Ashley B.
• Format: Article
• Language: English
• Subjects: ACTH-Secreting Pituitary Adenoma - chemistry; Adenoma - chemistry; Biological and medical sciences; Case-Control Studies; DNA Mutational Analysis; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Growth Hormone-Secreting Pituitary Adenoma - chemistry; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary Neoplasms - chemistry; Polymerase Chain Reaction - methods; Prolactinoma - chemistry; Proto-Oncogene Proteins B-raf - genetics; RNA, Messenger - analysis; Statistics, Nonparametric; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2006.02735.x

Summary 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. Design and measurements  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.